2-Morpholino-4-oxo-4,5-dihydro­thio­phene-3-carbonitrile

Zhu, J.J.; Liu, K.K.; Marx, M.A.; Rheingold, A.L.; Yanovsky, A.

doi:10.1107/S1600536809041737

organic compounds

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ISSN: 2056-9890

Volume 65| Part 11| November 2009| Page o2765

https://doi.org/10.1107/S1600536809041737

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2-Morpholino-4-oxo-4,5-dihydrothiophene-3-carbonitrile

JinJiang Zhu,^a Kevin K. Liu,^a Matthew A. Marx,^a Arnold L. Rheingold ^b and Alex Yanovsky ^a ^*

^aPfizer Global Research and Development, La Jolla Labs, 10770 Science Center Drive, San Diego, CA 92121, USA, and ^bDepartment of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
^*Correspondence e-mail: alex.yanovsky@pfizer.com

(Received 9 October 2009; accepted 12 October 2009; online 17 October 2009)

The title compound, C₉H₁₀N₂O₂S, was obtained from the treatment of ethyl 4-cyano-3-hydroxy-5-morpholinothiophene-2-carboxylate with concentrated HCl. The mean plane of the essentially planar dihydrothiophene ring is almost orthogonal to the mirror plane of the N-morpholine substituent, making a dihedral angle of 87.2 (2)°.

Related literature

For the structure of a similar compound with the morpholine substituent attached to dihydrothiophene ring, see: Moghaddam et al. (2005 ).

Experimental

Crystal data

C₉H₁₀N₂O₂S
M_r = 210.25
Monoclinic, P 2₁ /c
a = 7.1931 (3) Å
b = 17.3275 (8) Å
c = 7.2793 (3) Å
β = 94.506 (2)°
V = 904.48 (7) Å³
Z = 4
Cu Kα radiation
μ = 2.98 mm⁻¹
T = 100 K
0.41 × 0.20 × 0.08 mm

Data collection

Bruker Kappa APEXII diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2001 ) T_min = 0.765, T_max = 0.919
7337 measured reflections
1607 independent reflections
1531 reflections with I > 2σ(I)
R_int = 0.027

Refinement

R[F² > 2σ(F²)] = 0.026
wR(F²) = 0.068
S = 1.08
1607 reflections
128 parameters
H-atom parameters constrained
Δρ_max = 0.29 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Data collection: APEX2 (Bruker, 2007 ); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT; 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 pflj124, I. DOI: https://doi.org/10.1107/S1600536809041737/dn2498sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536809041737/dn2498Isup2.hkl

checkCIF report

Comment top

The title compound was obtained via the treatment of ethyl 4-cyano-3-hydroxy-5-morpholinothiophene-2-carboxylate with concentrated HCl, and its structural formula was confirmed by the present study (Fig. 1).

Dihydrothiophene ring C5/C6/C7/C8/S1 is planar within 0.02 Å. Its least squares plane is almost orthogonal to the mirror plane of the N-morpholine substituent passing through C5, N1 and O1 atoms: the corresponding dihedral angle being 92.8 (2)°. Similar conformation is observed in the related structure with morpholine substituent attached to dihydrothiophene ring (Moghaddam et al., 2005).

Related literature top

For the structure of a similar compound with the morpholine substituent attached to dihydrothiophene ring, see: Moghaddam et al. (2005).

Experimental top

Into a suspension of ethyl 4-cyano-3-hydroxy-5-morpholinothiophene-2-carboxylate (100 mg, 0.35 mmol) in MeOH (1.2 ml), was added concentrated HCl (0.2 ml) with stirring. The reaction mixture was heated in an oil bath at 60°C for 48 h to form a clear solution. The reaction solution was cooled to room temperature and the solvent was removed under reduced pressure. The resulting residue was neutralized with 2 N NaOH to pH 4. The precipitate was collected by filtration and rinsed with a solution of water/MeOH. The sample was dried under high vacuum to afford the desired compound as a white solid (52.1 mg, 58% yield). LC—MS (APCI, M+1) 211.2; ¹H NMR (300 MHz, DMSO-d₆) δ p.p.m. 3.87 (s, 3 H), 3.84 (dd, J=5.84, 2.07 Hz, 2 H), 3.68 - 3.79 (m, 5 H). The product was recrystallized from EtOAc/hexane/dichloromethane to yield single crystals suitable for X-ray diffraction studies.

Structure description top

For the structure of a similar compound with the morpholine substituent attached to dihydrothiophene ring, see: Moghaddam et al. (2005).

Computing details top

Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); 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 title compound, showing 50% probability displacement ellipsoids and atom numbering scheme. H atoms are drawn as circles with arbitrary small radius.

2-Morpholino-4-oxo-4,5-dihydrothiophene-3-carbonitrile top

Crystal data top

C₉H₁₀N₂O₂S	F(000) = 440
M_r = 210.25	D_x = 1.544 Mg m⁻³
Monoclinic, P2₁/c	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: -P 2ybc	Cell parameters from 2017 reflections
a = 7.1931 (3) Å	θ = 8.0–49.4°
b = 17.3275 (8) Å	µ = 2.98 mm⁻¹
c = 7.2793 (3) Å	T = 100 K
β = 94.506 (2)°	Blade, colorless
V = 904.48 (7) Å³	0.41 × 0.20 × 0.08 mm
Z = 4

Data collection top

Bruker Kappa APEXII diffractometer	1607 independent reflections
Radiation source: fine-focus sealed tube	1531 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.027
phi and ω scans	θ_max = 68.3°, θ_min = 5.1°
Absorption correction: multi-scan (SADABS; Bruker, 2001)	h = −7→8
T_min = 0.765, T_max = 0.919	k = −20→20
7337 measured reflections	l = −6→8

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)] = 0.026	H-atom parameters constrained
wR(F²) = 0.068	w = 1/[σ²(F_o²) + (0.0333P)² + 0.4P] where P = (F_o² + 2F_c²)/3
S = 1.08	(Δ/σ)_max = 0.005
1607 reflections	Δρ_max = 0.29 e Å⁻³
128 parameters	Δρ_min = −0.20 e Å⁻³
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0051 (4)

Crystal data top

C₉H₁₀N₂O₂S	V = 904.48 (7) Å³
M_r = 210.25	Z = 4
Monoclinic, P2₁/c	Cu Kα radiation
a = 7.1931 (3) Å	µ = 2.98 mm⁻¹
b = 17.3275 (8) Å	T = 100 K
c = 7.2793 (3) Å	0.41 × 0.20 × 0.08 mm
β = 94.506 (2)°

Data collection top

Bruker Kappa APEXII diffractometer	1607 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2001)	1531 reflections with I > 2σ(I)
T_min = 0.765, T_max = 0.919	R_int = 0.027
7337 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.026	0 restraints
wR(F²) = 0.068	H-atom parameters constrained
S = 1.08	Δρ_max = 0.29 e Å⁻³
1607 reflections	Δρ_min = −0.20 e Å⁻³
128 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	0.41531 (4)	0.190051 (19)	0.14477 (4)	0.01446 (13)
O1	0.93155 (14)	−0.01397 (6)	0.25143 (14)	0.0203 (2)
O2	0.60927 (14)	0.39685 (6)	0.22161 (14)	0.0206 (2)
N2	1.03469 (17)	0.30903 (7)	0.41842 (18)	0.0206 (3)
N1	0.72767 (15)	0.12491 (7)	0.28592 (16)	0.0153 (3)
C3	0.7576 (2)	−0.00224 (8)	0.1488 (2)	0.0202 (3)
H3A	0.6948	−0.0526	0.1261	0.024*
H3B	0.7789	0.0210	0.0281	0.024*
C4	0.63342 (19)	0.05034 (8)	0.2519 (2)	0.0186 (3)
H4A	0.5133	0.0583	0.1783	0.022*
H4B	0.6072	0.0263	0.3706	0.022*
C5	0.64590 (18)	0.19201 (8)	0.24689 (18)	0.0127 (3)
C6	0.71300 (18)	0.26741 (8)	0.27408 (17)	0.0132 (3)
C7	0.58227 (19)	0.32720 (8)	0.21546 (17)	0.0143 (3)
C9	0.89130 (19)	0.28941 (8)	0.35321 (18)	0.0147 (3)
C8	0.39555 (18)	0.29364 (8)	0.14293 (18)	0.0163 (3)
H8A	0.3622	0.3121	0.0159	0.020*
H8B	0.2968	0.3101	0.2218	0.020*
C2	1.0259 (2)	0.05782 (8)	0.2777 (2)	0.0204 (3)
H2A	1.0490	0.0799	0.1562	0.025*
H2B	1.1482	0.0491	0.3468	0.025*
C1	0.91428 (19)	0.11467 (8)	0.3821 (2)	0.0191 (3)
H1A	0.9019	0.0954	0.5086	0.023*
H1B	0.9799	0.1649	0.3912	0.023*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.01039 (19)	0.0182 (2)	0.0144 (2)	−0.00046 (11)	−0.00152 (13)	−0.00068 (11)
O1	0.0208 (5)	0.0133 (5)	0.0264 (5)	0.0025 (4)	−0.0004 (4)	0.0007 (4)
O2	0.0198 (5)	0.0151 (5)	0.0270 (5)	0.0026 (4)	0.0030 (4)	0.0025 (4)
N2	0.0156 (6)	0.0184 (6)	0.0273 (7)	−0.0014 (5)	−0.0015 (5)	−0.0033 (5)
N1	0.0123 (5)	0.0139 (6)	0.0191 (6)	−0.0009 (4)	−0.0025 (5)	−0.0008 (4)
C3	0.0230 (8)	0.0154 (7)	0.0216 (7)	−0.0006 (5)	−0.0021 (6)	−0.0011 (5)
C4	0.0162 (7)	0.0139 (7)	0.0253 (7)	−0.0039 (5)	−0.0008 (6)	−0.0010 (5)
C5	0.0111 (6)	0.0169 (7)	0.0102 (6)	0.0006 (5)	0.0018 (5)	−0.0011 (5)
C6	0.0118 (6)	0.0149 (7)	0.0129 (6)	0.0007 (5)	0.0014 (5)	−0.0003 (5)
C7	0.0142 (6)	0.0174 (7)	0.0118 (6)	0.0011 (5)	0.0040 (5)	0.0008 (5)
C9	0.0167 (7)	0.0116 (6)	0.0161 (6)	0.0015 (5)	0.0036 (5)	−0.0006 (5)
C8	0.0135 (7)	0.0193 (7)	0.0159 (7)	0.0031 (5)	−0.0001 (5)	0.0011 (5)
C2	0.0158 (7)	0.0160 (7)	0.0293 (8)	0.0006 (5)	0.0008 (6)	0.0049 (6)
C1	0.0147 (7)	0.0145 (7)	0.0267 (7)	0.0004 (5)	−0.0071 (6)	0.0005 (5)

Geometric parameters (Å, º) top

S1—C5	1.7639 (13)	C4—H4B	0.9900
S1—C8	1.8004 (14)	C5—C6	1.4014 (18)
O1—C3	1.4204 (17)	C6—C9	1.4163 (18)
O1—C2	1.4227 (17)	C6—C7	1.4410 (18)
O2—C7	1.2227 (17)	C7—C8	1.5197 (18)
N2—C9	1.1523 (19)	C8—H8A	0.9900
N1—C5	1.3238 (17)	C8—H8B	0.9900
N1—C4	1.4710 (17)	C2—C1	1.513 (2)
N1—C1	1.4751 (17)	C2—H2A	0.9900
C3—C4	1.515 (2)	C2—H2B	0.9900
C3—H3A	0.9900	C1—H1A	0.9900
C3—H3B	0.9900	C1—H1B	0.9900
C4—H4A	0.9900

C5—S1—C8	93.15 (6)	O2—C7—C6	126.92 (13)
C3—O1—C2	109.68 (10)	O2—C7—C8	121.60 (12)
C5—N1—C4	122.97 (11)	C6—C7—C8	111.48 (12)
C5—N1—C1	125.44 (11)	N2—C9—C6	178.37 (15)
C4—N1—C1	111.37 (11)	C7—C8—S1	108.17 (9)
O1—C3—C4	110.79 (11)	C7—C8—H8A	110.1
O1—C3—H3A	109.5	S1—C8—H8A	110.1
C4—C3—H3A	109.5	C7—C8—H8B	110.1
O1—C3—H3B	109.5	S1—C8—H8B	110.1
C4—C3—H3B	109.5	H8A—C8—H8B	108.4
H3A—C3—H3B	108.1	O1—C2—C1	111.75 (11)
N1—C4—C3	109.24 (11)	O1—C2—H2A	109.3
N1—C4—H4A	109.8	C1—C2—H2A	109.3
C3—C4—H4A	109.8	O1—C2—H2B	109.3
N1—C4—H4B	109.8	C1—C2—H2B	109.3
C3—C4—H4B	109.8	H2A—C2—H2B	107.9
H4A—C4—H4B	108.3	N1—C1—C2	109.81 (11)
N1—C5—C6	130.26 (12)	N1—C1—H1A	109.7
N1—C5—S1	117.43 (10)	C2—C1—H1A	109.7
C6—C5—S1	112.30 (10)	N1—C1—H1B	109.7
C5—C6—C9	126.81 (12)	C2—C1—H1B	109.7
C5—C6—C7	114.77 (12)	H1A—C1—H1B	108.2
C9—C6—C7	118.42 (12)

Experimental details

Crystal data
Chemical formula	C₉H₁₀N₂O₂S
M_r	210.25
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	100
a, b, c (Å)	7.1931 (3), 17.3275 (8), 7.2793 (3)
β (°)	94.506 (2)
V (Å³)	904.48 (7)
Z	4
Radiation type	Cu Kα
µ (mm⁻¹)	2.98
Crystal size (mm)	0.41 × 0.20 × 0.08

Data collection
Diffractometer	Bruker Kappa APEXII
Absorption correction	Multi-scan (SADABS; Bruker, 2001)
T_min, T_max	0.765, 0.919
No. of measured, independent and observed [I > 2σ(I)] reflections	7337, 1607, 1531
R_int	0.027
(sin θ/λ)_max (Å⁻¹)	0.603

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.026, 0.068, 1.08
No. of reflections	1607
No. of parameters	128
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.29, −0.20

Computer programs: APEX2 (Bruker, 2007), SAINT (Bruker, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

References

Bruker (2001). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Bruker (2007). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Moghaddam, F. M., Boeini, H. Z., Bagheri, M., Ruëdi, P. & Linden, A. (2005). Sulfur Chem. 26, 245–250. CSD CrossRef CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar