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

Dayananda, A.S.; Jasinski, J.P.; Golen, J.A.; Yathirajan, H.S.; Narayana, B.

doi:10.1107/S1600536811031199

organic compounds

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Volume 67| Part 9| September 2011| Page o2271

doi:10.1107/S1600536811031199

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

A. S. Dayananda,^a Jerry P. Jasinski,^b ^* James A. Golen,^b H. S. Yathirajan ^a and B. Narayana ^c

^aDepartment of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, India, ^bDepartment of Chemistry, Keene State College, 229 Main Street, Keene, NH 03435-2001, USA, and ^cDepartment of Studies in Chemistry, Mangalore University, Mangalagangotri, 574 199, India
^*Correspondence e-mail: jjasinski@keene.edu

(Received 1 August 2011; accepted 2 August 2011; online 6 August 2011)

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, P 2₁ /n
a = 5.8663 (3) Å
b = 27.0109 (9) Å
c = 7.1385 (4) Å
β = 110.767 (6)°
V = 1057.63 (9) Å³
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 $[Oxford Diffraction (2010). CrysAlis PRO and CrysAlis RED. Oxford Diffraction Ltd, Yarnton, England.]$ ) 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[F² > 2σ(F²)] = 0.038
wR(F²) = 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

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) $[x+{\script{1\over 2}}, -y+{\script{1\over 2}}, z-{\script{1\over 2}}]$ ; (ii) $[x-{\script{3\over 2}}, -y-{\script{1\over 2}}, z-{\script{3\over 2}}]$ .

Data collection: CrysAlis PRO (Oxford Diffraction, 2010 $[Oxford Diffraction (2010). CrysAlis PRO and CrysAlis RED. Oxford Diffraction Ltd, Yarnton, England.]$ ); cell refinement: CrysAlis PRO; data reduction: CrysAlis RED (Oxford Diffraction, 2010 $[Oxford Diffraction (2010). CrysAlis PRO and CrysAlis RED. Oxford Diffraction Ltd, Yarnton, England.]$ ); 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.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811031199/tk2775sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536811031199/tk2775Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536811031199/tk2775Isup3.cml

checkCIF report

Comment top

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..Cg π-ring intermolecular interactions (Table 1) forming a 2-D supramolecular layer which stacks along the b axis (Fig. 2).

Related literature top

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 top

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).

Computing details top

Data collection: CrysAlis PRO (Oxford Diffraction, 2010); cell refinement: CrysAlis PRO (Oxford Diffraction, 2010); 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 (Sheldrick, 2008).

Figures top

	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.

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

Crystal data top

C₉H₁₄NOS⁺·Cl⁻	F(000) = 464
M_r = 219.72	D_x = 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 top

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

Refinement top

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(F_o²) + (0.0412P)² + 0.4408P] where P = (F_o² + 2F_c²)/3
S = 1.13	(Δ/σ)_max = 0.003
3538 reflections	Δρ_max = 0.37 e Å⁻³
124 parameters	Δρ_min = −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)

Crystal data top

C₉H₁₄NOS⁺·Cl⁻	V = 1057.63 (9) Å³
M_r = 219.72	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 5.8663 (3) Å	µ = 0.52 mm⁻¹
b = 27.0109 (9) Å	T = 173 K
c = 7.1385 (4) Å	0.24 × 0.21 × 0.11 mm
β = 110.767 (6)°

Data collection top

Oxford Diffraction Xcalibur Eos Gemini diffractometer	3538 independent reflections
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2010)	3290 reflections with I > 2σ(I)
T_min = 0.885, T_max = 0.945	R_int = 0.033
14443 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.038	1 restraint
wR(F²) = 0.097	H atoms treated by a mixture of independent and constrained refinement
S = 1.13	Δρ_max = 0.37 e Å⁻³
3538 reflections	Δρ_min = −0.28 e Å⁻³
124 parameters

Special details top

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 (Å²) top

	x	y	z	U_iso*/U_eq
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 (Å²) top

	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, º) top

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, º) top

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.

Experimental details

Crystal data
Chemical formula	C₉H₁₄NOS⁺·Cl⁻
M_r	219.72
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	173
a, b, c (Å)	5.8663 (3), 27.0109 (9), 7.1385 (4)
β (°)	110.767 (6)
V (Å³)	1057.63 (9)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.52
Crystal size (mm)	0.24 × 0.21 × 0.11

Data collection
Diffractometer	Oxford Diffraction Xcalibur Eos Gemini diffractometer
Absorption correction	Multi-scan (CrysAlis RED; Oxford Diffraction, 2010)
T_min, T_max	0.885, 0.945
No. of measured, independent and observed [I > 2σ(I)] reflections	14443, 3538, 3290
R_int	0.033
(sin θ/λ)_max (Å⁻¹)	0.751

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.038, 0.097, 1.13
No. of reflections	3538
No. of parameters	124
No. of restraints	1
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.37, −0.28

Computer programs: CrysAlis PRO (Oxford Diffraction, 2010), CrysAlis RED (Oxford Diffraction, 2010), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

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	0.870 (13)	2.170 (14)	3.0317 (11)	170.7 (15)
C1—H1A···Cl1ⁱ	0.95	2.82	3.5641 (13)	136.2
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.

Acknowledgements

ASD thanks the University of Mysore for research facilities. JPJ acknowledges the NSF–MRI program (grant No. CHE-1039027) for funds to purchase the X-ray diffractometer.

References

Bhadbhade, M., Hook, J., Marjo, C., Rich, A. & Lin, Q. (2009). Acta Cryst. E65, o2294. CSD CrossRef IUCr Journals Google Scholar
Gupta, S., Nihalani, N. & Masand, P. (2007). Ann. Clin. Psychiatry, 19, 125–132. CrossRef Google Scholar
Oxford Diffraction (2010). CrysAlis PRO and CrysAlis RED. Oxford Diffraction Ltd, Yarnton, England. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Tao, 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
Tao, X., Zhang, X.-Q., Yuan, L. & Wang, J.-T. (2008). Acta Cryst. E64, o553. Web of Science CSD CrossRef IUCr Journals Google Scholar
Waitekus, A. B. & Kirkpatrick, P. (2004). Nat. Rev. Drug Discov. 3, 907–908. Web of Science CrossRef PubMed CAS Google Scholar

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doi:10.1107/S1600536811031199

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