N,N-Dimethyl-3-oxo-3-(thio­phen-2-yl)propanaminium chloride

Abstract

In the title mol­ecular salt, C₉H₁₄NOS⁺·Cl⁻, the crystal packing is stabilized by weak inter­molecular N—H⋯Cl, C—H⋯Cl and C—H⋯π inter­actions, which lead to the formation of a two-dimensional supra­molecular layer which stacks along the b axis.

Related literature

For the management of major depressive disorders, see: Gupta et al. (2007 ▶). For the dual re-uptake inhibitor drug, duloxetine [systematic name (+)-(S)-N-methyl-3-(naphthalen-1-yl­oxy)-3-(thio­phen-2-yl)propan-1-amine], see: Waitekus & Kirkpatrick, (2004 ▶). For related structures, see: Bhadbhade et al. (2009 ▶); Tao et al. (2006 ▶, 2008 ▶).

Experimental

Crystal data

• C₉H₁₄NOS⁺·Cl⁻

• M _r = 219.72

• Monoclinic,

• a = 5.8663 (3) Å

• b = 27.0109 (9) Å

• c = 7.1385 (4) Å

• β = 110.767 (6)°

• V = 1057.63 (9) ų

• Z = 4

• Mo Kα radiation

• μ = 0.52 mm⁻¹

• T = 173 K

• 0.24 × 0.21 × 0.11 mm

Data collection

• Oxford Diffraction Xcalibur Eos Gemini diffractometer

• Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2010 ▶) T _min = 0.885, T _max = 0.945

• 14443 measured reflections

• 3538 independent reflections

• 3290 reflections with I > 2σ(I)

• R _int = 0.033

Refinement

• R[F ² > 2σ(F ²)] = 0.038

• wR(F ²) = 0.097

• S = 1.13

• 3538 reflections

• 124 parameters

• 1 restraint

• H atoms treated by a mixture of independent and constrained refinement

• Δρ_max = 0.37 e Å⁻³

• Δρ_min = −0.28 e Å⁻³

Data collection: CrysAlis PRO (Oxford Diffraction, 2010 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis RED (Oxford Diffraction, 2010 ▶); 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

Supplementary material file. DOI: 10.1107/S1600536811031199/tk2775Isup3.cml

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

Table 1. Hydrogen-bond geometry (Å, °).

Cg1 is the centroid of the S1/C1–C4 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1N⋯Cl1	0.87 (1)	2.17 (1)	3.0317 (11)	171 (2)
C1—H1A⋯Cl1i	0.95	2.82	3.5641 (13)	136
C6—H6A⋯Cg1ii	0.99	2.97	3.8183 (13)	144

Symmetry codes: (i) ; (ii) .

supplementary crystallographic information

Comment

The title salt, (I), C₉H₁₄NOS⁺, Cl^-, is an intermediate in the synthesis of duloxetine, which is a new generation drug indicated for the management of major depressive disorders as well as for neuropathic pain (Waitekus & Kirkpatrick, 2004). Duloxetine is a dual re-uptake inhibitor with actions on serotonin as well as norepinephrine (Gupta et al., 2007). The crystal structures of related structures, (R)-3-hydroxy-N,N-dimethyl-3-(2-thienyl)-propanamine (Tao et al., 2006), N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propan-1-amine (Tao et al., 2008) and duloxetine hydrochloride (Bhadbhade et al., 2009) have been reported. In view of the importance of duloxetine, the crystal structure of the title compound, (I), is reported.

In the molecular salt, C₉H₁₄NOS⁺, Cl^-, one cation-anion pair makes up the asymmetric unit (Fig. 1). The crystal packing is stabilized by weak N—H···Cl, C—H···Cl and C—H..Cgπ-ring intermolecular interactions (Table 1) forming a 2-D supramolecular layer which stacks along the b axis (Fig. 2).

Experimental

The title compound was obtained as a gift sample from R. L. Fine chem., Bangalore. X-ray quality crystals were obtained from slow evaporation of methanol solution (M.pt.: 451–454 K).

Refinement

The N—H atom was located from a difference Fourier map and refined with N—H = 0.87±0.02 Å, and with U_iso(H) = 1.19U_eq(N). All of the remaining H atoms were placed in their calculated positions and then refined using the riding model with C—H lengths of 0.95 Å (CH), 0.99 Å (CH₂) or 0.98 Å (CH₃). The isotropic displacement parameters for these atoms were set to 1.20 (CH), 1.19 (CH₂) or 1.49–1.51 (CH₃) times U_eq of the parent atom.

Figures

Fig. 1.

Molecular structure of the ion pair in the title compound showing the atom labeling scheme and 50% probability displacement ellipsoids.

Fig. 2.

Packing diagram of the title compound viewed down the a axis. Dashed lines indicate weak N—H···Cl and C—H···Cl intermolecular interactions forming a 2-D supramolecular layer which stacks along the b axis.

Crystal data

C9H14NOS+·Cl−	F(000) = 464
Mr = 219.72	Dx = 1.380 Mg m−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 6745 reflections
a = 5.8663 (3) Å	θ = 3.1–32.2°
b = 27.0109 (9) Å	µ = 0.52 mm−1
c = 7.1385 (4) Å	T = 173 K
β = 110.767 (6)°	Block, colorless
V = 1057.63 (9) Å3	0.24 × 0.21 × 0.11 mm
Z = 4

Data collection

Oxford Diffraction Xcalibur Eos Gemini diffractometer	3538 independent reflections
Radiation source: Enhance (Mo) X-ray Source	3290 reflections with I > 2σ(I)
graphite	Rint = 0.033
Detector resolution: 16.1500 pixels mm-1	θmax = 32.3°, θmin = 3.1°
ω scans	h = −8→8
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2010)	k = −39→40
Tmin = 0.885, Tmax = 0.945	l = −10→10
14443 measured reflections

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)] = 0.038	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.097	w = 1/[σ2(Fo2) + (0.0412P)2 + 0.4408P] where P = (Fo2 + 2Fc2)/3
S = 1.13	(Δ/σ)max = 0.003
3538 reflections	Δρmax = 0.37 e Å−3
124 parameters	Δρmin = −0.28 e Å−3
1 restraint	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0190 (18)

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq
S1	0.52202 (6)	0.201976 (12)	0.22248 (5)	0.02281 (9)
Cl1	0.25260 (7)	0.437297 (12)	0.73047 (5)	0.02698 (10)
O1	0.59639 (18)	0.31119 (4)	0.23658 (16)	0.0269 (2)
N1	0.1628 (2)	0.42989 (4)	0.28618 (16)	0.0202 (2)
H1N	0.185 (3)	0.4283 (6)	0.413 (2)	0.024*
C1	0.3315 (2)	0.15653 (5)	0.24400 (19)	0.0232 (2)
H1A	0.3584	0.1222	0.2307	0.028*
C2	0.1360 (2)	0.17494 (5)	0.2825 (2)	0.0232 (2)
H2A	0.0125	0.1549	0.3008	0.028*
C3	0.1380 (2)	0.22742 (4)	0.29226 (19)	0.0200 (2)
H3A	0.0157	0.2465	0.3172	0.024*
C4	0.3377 (2)	0.24739 (4)	0.26137 (17)	0.0176 (2)
C5	0.4056 (2)	0.29935 (4)	0.25738 (17)	0.0183 (2)
C6	0.2273 (2)	0.33779 (4)	0.27755 (18)	0.0193 (2)
H6A	0.0631	0.3312	0.1780	0.023*
H6B	0.2174	0.3358	0.4129	0.023*
C7	0.3098 (2)	0.38907 (4)	0.24408 (19)	0.0209 (2)
H7A	0.4826	0.3934	0.3311	0.025*
H7B	0.3006	0.3918	0.1033	0.025*
C8	−0.1028 (3)	0.42606 (5)	0.1722 (2)	0.0301 (3)
H8A	−0.1859	0.4550	0.2009	0.045*
H8B	−0.1665	0.3959	0.2118	0.045*
H8C	−0.1313	0.4248	0.0284	0.045*
C9	0.2585 (3)	0.47836 (5)	0.2479 (2)	0.0278 (3)
H9A	0.1668	0.5052	0.2806	0.042*
H9B	0.2405	0.4806	0.1063	0.042*
H9C	0.4313	0.4812	0.3315	0.042*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
S1	0.01902 (15)	0.02573 (16)	0.02610 (16)	0.00399 (11)	0.01097 (12)	−0.00015 (11)
Cl1	0.03912 (19)	0.02268 (15)	0.02328 (15)	−0.00231 (12)	0.01617 (13)	−0.00105 (11)
O1	0.0213 (4)	0.0274 (5)	0.0360 (5)	−0.0029 (4)	0.0150 (4)	−0.0012 (4)
N1	0.0250 (5)	0.0182 (4)	0.0199 (5)	−0.0021 (4)	0.0109 (4)	−0.0013 (4)
C1	0.0259 (6)	0.0205 (5)	0.0226 (6)	0.0040 (4)	0.0078 (5)	0.0007 (4)
C2	0.0221 (6)	0.0213 (5)	0.0265 (6)	−0.0012 (4)	0.0090 (5)	0.0012 (5)
C3	0.0169 (5)	0.0199 (5)	0.0243 (5)	0.0010 (4)	0.0086 (4)	0.0001 (4)
C4	0.0149 (5)	0.0197 (5)	0.0174 (5)	0.0016 (4)	0.0050 (4)	0.0003 (4)
C5	0.0173 (5)	0.0221 (5)	0.0156 (5)	−0.0002 (4)	0.0060 (4)	−0.0002 (4)
C6	0.0187 (5)	0.0196 (5)	0.0209 (5)	−0.0008 (4)	0.0086 (4)	0.0006 (4)
C7	0.0228 (5)	0.0200 (5)	0.0234 (5)	−0.0008 (4)	0.0126 (5)	−0.0007 (4)
C8	0.0240 (6)	0.0232 (6)	0.0421 (8)	0.0012 (5)	0.0106 (6)	−0.0032 (5)
C9	0.0377 (7)	0.0177 (5)	0.0315 (7)	−0.0056 (5)	0.0167 (6)	−0.0020 (5)

Geometric parameters (Å, °)

S1—C1	1.7032 (14)	C4—C5	1.4620 (16)
S1—C4	1.7216 (12)	C5—C6	1.5165 (16)
O1—C5	1.2224 (15)	C6—C7	1.5139 (16)
N1—C8	1.4834 (18)	C6—H6A	0.9900
N1—C9	1.4876 (16)	C6—H6B	0.9900
N1—C7	1.4947 (16)	C7—H7A	0.9900
N1—H1N	0.870 (13)	C7—H7B	0.9900
C1—C2	1.3647 (18)	C8—H8A	0.9800
C1—H1A	0.9500	C8—H8B	0.9800
C2—C3	1.4191 (17)	C8—H8C	0.9800
C2—H2A	0.9500	C9—H9A	0.9800
C3—C4	1.3769 (16)	C9—H9B	0.9800
C3—H3A	0.9500	C9—H9C	0.9800
C1—S1—C4	91.69 (6)	C7—C6—H6A	109.7
C8—N1—C9	110.60 (11)	C5—C6—H6A	109.7
C8—N1—C7	114.01 (10)	C7—C6—H6B	109.7
C9—N1—C7	109.27 (10)	C5—C6—H6B	109.7
C8—N1—H1N	108.0 (12)	H6A—C6—H6B	108.2
C9—N1—H1N	107.8 (11)	N1—C7—C6	113.80 (9)
C7—N1—H1N	106.8 (11)	N1—C7—H7A	108.8
C2—C1—S1	112.38 (10)	C6—C7—H7A	108.8
C2—C1—H1A	123.8	N1—C7—H7B	108.8
S1—C1—H1A	123.8	C6—C7—H7B	108.8
C1—C2—C3	112.40 (11)	H7A—C7—H7B	107.7
C1—C2—H2A	123.8	N1—C8—H8A	109.5
C3—C2—H2A	123.8	N1—C8—H8B	109.5
C4—C3—C2	112.10 (11)	H8A—C8—H8B	109.5
C4—C3—H3A	124.0	N1—C8—H8C	109.5
C2—C3—H3A	124.0	H8A—C8—H8C	109.5
C3—C4—C5	129.24 (11)	H8B—C8—H8C	109.5
C3—C4—S1	111.43 (9)	N1—C9—H9A	109.5
C5—C4—S1	119.33 (9)	N1—C9—H9B	109.5
O1—C5—C4	121.40 (11)	H9A—C9—H9B	109.5
O1—C5—C6	121.64 (11)	N1—C9—H9C	109.5
C4—C5—C6	116.96 (10)	H9A—C9—H9C	109.5
C7—C6—C5	109.97 (9)	H9B—C9—H9C	109.5
C4—S1—C1—C2	−0.93 (11)	S1—C4—C5—O1	−3.55 (17)
S1—C1—C2—C3	0.86 (15)	C3—C4—C5—C6	−4.03 (19)
C1—C2—C3—C4	−0.29 (16)	S1—C4—C5—C6	175.70 (8)
C2—C3—C4—C5	179.34 (12)	O1—C5—C6—C7	6.42 (16)
C2—C3—C4—S1	−0.40 (14)	C4—C5—C6—C7	−172.82 (10)
C1—S1—C4—C3	0.75 (10)	C8—N1—C7—C6	−55.48 (14)
C1—S1—C4—C5	−179.02 (10)	C9—N1—C7—C6	−179.79 (11)
C3—C4—C5—O1	176.73 (13)	C5—C6—C7—N1	−172.73 (10)

Hydrogen-bond geometry (Å, °)

Cg1 is the centroid of the S1/C1–C4 ring.

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···Cl1	0.87 (1)	2.17 (1)	3.0317 (11)	171.(2)
C1—H1A···Cl1i	0.95	2.82	3.5641 (13)	136.
C6—H6A···Cg1ii	0.99	2.97	3.8183 (13)	144

Symmetry codes: (i) x+1/2, −y+1/2, z−1/2; (ii) x−3/2, −y−1/2, z−3/2.