1-(Morpholino­meth­yl)indoline-2,3-dione

Tang, Y.; Zhang, J.; Miao, Y.; Chen, G.

doi:10.1107/S1600536810023160

organic compounds

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ISSN: 2056-9890

Volume 66| Part 7| July 2010| Page o1748

doi:10.1107/S1600536810023160

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1-(Morpholinomethyl)indoline-2,3-dione

Ying Tang,^a Jie Zhang,^a Yanqing Miao ^b and Gang Chen ^a ^*

^aCollege of Chemistry and Chemical Engineering, Xi'an Shiyou University, Second Dianzi Road, Xi'an 710065, People's Republic of China, and ^bDepartment of Pharmacy, Xi'an Medical University, Hanguang Round 137, Xi'an 710021, People's Republic of China
^*Correspondence e-mail: cg1014@126.com

(Received 29 May 2010; accepted 15 June 2010; online 23 June 2010)

In the title compound, C₁₃H₁₄N₂O₃, the morpholine ring displays a chair conformation, with the (2,3-dioxoindolin-1-yl)methyl group in an equatorial position. The crystal structure is stabilized by intermolecular C—H⋯O hydrogen bonds.

Related literature

For the synthesis of isatin-N-Mannich bases, see: Varma & Nobles ((1966 ). For the bioactivity of isatin derivatives, see: Glover et al. (1980 , 1988 ); Maysinger et al. (1980 ).

Experimental

Crystal data

C₁₃H₁₄N₂O₃
M_r = 246.26
Monoclinic, P 2₁ /c
a = 11.608 (2) Å
b = 8.2818 (17) Å
c = 12.595 (3) Å
β = 100.20 (3)°
V = 1191.7 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 293 K
0.26 × 0.18 × 0.16 mm

Data collection

Bruker SMART CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2001 ) T_min = 0.979, T_max = 0.984
7614 measured reflections
3556 independent reflections
2275 reflections with I > 2σ(I)
R_int = 0.021

Refinement

R[F² > 2σ(F²)] = 0.042
wR(F²) = 0.144
S = 0.99
3556 reflections
171 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.19 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C6—H6A⋯O1ⁱ	0.93	2.47	3.349 (2)	158
C5—H5A⋯O2ⁱⁱ	0.93	2.52	3.216 (2)	131
Symmetry codes: (i) $[x, -y+{\script{1\over 2}}, z+{\script{1\over 2}}]$ ; (ii) $[x, -y+{\script{3\over 2}}, z+{\script{1\over 2}}]$ .

Data collection: SMART (Bruker, 2001); cell refinement: SAINT-Plus (Bruker, 2001); data reduction: SAINT-Plus; 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 I, global. DOI: 10.1107/S1600536810023160/rz2460sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536810023160/rz2460Isup2.hkl

checkCIF report

Comment top

Isatin has draw great attention from being discovered as a component of endogenous monoamine oxidase (MAO) inhibitory activity (tribulin) and subsequently identified as a selective inhibitor of MAO B at low concentrations (Glover et al., 1980, 1988). In the following years, many isatin derivatives, such as isatin hydrazono, isatin Mannich bases and isatin based spiroazetidinones, have also been reported to possess anticonvulsant activity (Maysinger, et al., 1980). Herein we report the synthesis and crystal structure of the title compound.

The X-ray structural analysis confirmed the assignment of the structure from spectroscopic data. The molecular structure of the title compound is depicted in Fig. 1. Geometric parameters of the title compound are in the usual ranges. The morpholin ring displays a typical chair conformation, with the (2,3-dioxoindolin-1-yl)methyl group in equatorial position. In the crystal structure, the molecules are linked into a three-dimensional network by C—H···O hydrogen bonds (Table 1).

Related literature top

For the synthesis of isatin-N-Mannich bases, see: Varma & Nobles ((1966). For the bioactivity of isatin derivatives, see: Glover et al. (1980, 1988); Maysinger et al. (1980).

Experimental top

The title compound was synthesized according the literature method (Varma & Nobles, 1966). Isatin (1 mmol), formaldehyde (1.2 mmol) and morpholin (1.2 mmol) were dissolved in methanol (20 ml). The mixture was refluxed until the disappearance of isatin, as evidenced by thin-layer chromatography. The solvent was removed in vacuo and the residue was separated by column chromatography (silica gel, petroleum ether/ethyl acetate = 1:1 v/v), giving the title compound. ¹H-NMR (D₆—DMSO, 400 MHz): 7.61 (2H, m), 7.15 (1H, t, J = 7.2 Hz), 7.09 (1H, d, J = 8.0 Hz), 4.45 (2H, s), 3.70 (4H, t, J = 4.8 Hz), 2.63 (4H, t, J = 4.8 Hz); MS (EI) m/z: 246 (M⁺). 20 mg of the title compound was dissolved in 50 ml methanol and the solution was kept at room temperature for 4 d. Slow evaporation of the solvent gave orange single crystals of the title compound suitable for X-ray analysis.

Computing details top

Data collection: SMART (Bruker, 2001); cell refinement: SAINT-Plus (Bruker, 2001); data reduction: SAINT-Plus (Bruker, 2001); 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. An ORTEP-3 drawing of the title compound, with the atom-numbering scheme and 30% probability displacement ellipsoids.

1-(Morpholinomethyl)indoline-2,3-dione top

Crystal data top

C₁₃H₁₄N₂O₃	F(000) = 520
M_r = 246.26	D_x = 1.373 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 7356 reflections
a = 11.608 (2) Å	θ = 1.5–25.0°
b = 8.2818 (17) Å	µ = 0.10 mm⁻¹
c = 12.595 (3) Å	T = 293 K
β = 100.20 (3)°	Block, orange
V = 1191.7 (4) Å³	0.26 × 0.18 × 0.16 mm
Z = 4

Data collection top

Bruker SMART CCD diffractometer	3556 independent reflections
Radiation source: fine-focus sealed tube	2275 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.021
phi and ω scans	θ_max = 30.4°, θ_min = 1.8°
Absorption correction: multi-scan (SADABS; Bruker, 2001)	h = −15→15
T_min = 0.979, T_max = 0.984	k = −11→10
7614 measured reflections	l = −17→15

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.042	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.144	H atoms treated by a mixture of independent and constrained refinement
S = 0.99	w = 1/[σ²(F_o²) + (0.1P)²] where P = (F_o² + 2F_c²)/3
3556 reflections	(Δ/σ)_max = 0.039
171 parameters	Δρ_max = 0.19 e Å⁻³
0 restraints	Δρ_min = −0.22 e Å⁻³

Crystal data top

C₁₃H₁₄N₂O₃	V = 1191.7 (4) Å³
M_r = 246.26	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 11.608 (2) Å	µ = 0.10 mm⁻¹
b = 8.2818 (17) Å	T = 293 K
c = 12.595 (3) Å	0.26 × 0.18 × 0.16 mm
β = 100.20 (3)°

Data collection top

Bruker SMART CCD diffractometer	3556 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2001)	2275 reflections with I > 2σ(I)
T_min = 0.979, T_max = 0.984	R_int = 0.021
7614 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.042	0 restraints
wR(F²) = 0.144	H atoms treated by a mixture of independent and constrained refinement
S = 0.99	Δρ_max = 0.19 e Å⁻³
3556 reflections	Δρ_min = −0.22 e Å⁻³
171 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
N2	0.91766 (9)	0.23385 (12)	0.11391 (8)	0.0368 (3)
N1	0.73127 (8)	0.33226 (11)	0.00535 (8)	0.0347 (3)
C7	0.68098 (9)	0.48053 (14)	0.03062 (9)	0.0313 (3)
O2	0.59676 (8)	0.46330 (13)	−0.24949 (7)	0.0527 (3)
C10	0.98088 (11)	0.23531 (16)	0.02322 (11)	0.0414 (3)
H10A	0.9591	0.3302	−0.0209	0.050*
H10B	0.9604	0.1404	−0.0212	0.050*
O3	1.14402 (7)	0.37200 (13)	0.13337 (9)	0.0564 (3)
O1	0.73752 (10)	0.19019 (12)	−0.15122 (8)	0.0567 (3)
C6	0.68346 (10)	0.54811 (15)	0.13085 (10)	0.0379 (3)
H6A	0.7192	0.4957	0.1934	0.046*
C8	0.62332 (10)	0.55651 (14)	−0.06320 (9)	0.0345 (3)
C2	0.63447 (10)	0.45189 (15)	−0.15409 (10)	0.0377 (3)
C9	0.79252 (11)	0.21364 (15)	0.08256 (11)	0.0373 (3)
C5	0.63034 (11)	0.69807 (15)	0.13481 (11)	0.0456 (3)
H5A	0.6323	0.7477	0.2014	0.055*
C1	0.70789 (11)	0.30626 (15)	−0.10310 (10)	0.0385 (3)
C3	0.56961 (11)	0.70484 (16)	−0.05764 (11)	0.0444 (3)
H3A	0.5311	0.7557	−0.1197	0.053*
C13	0.95237 (11)	0.37262 (17)	0.18371 (11)	0.0435 (3)
H13A	0.9126	0.3692	0.2452	0.052*
H13B	0.9303	0.4718	0.1443	0.052*
C4	0.57469 (12)	0.77531 (16)	0.04263 (12)	0.0495 (4)
H4A	0.5403	0.8757	0.0481	0.059*
C12	1.08328 (12)	0.3691 (2)	0.22195 (12)	0.0540 (4)
H12A	1.1065	0.4616	0.2680	0.065*
H12B	1.1043	0.2721	0.2642	0.065*
C11	1.11103 (11)	0.23690 (17)	0.06581 (12)	0.0514 (4)
H11A	1.1329	0.1385	0.1062	0.062*
H11B	1.1529	0.2397	0.0057	0.062*
H9A	0.7745 (10)	0.1067 (17)	0.0422 (11)	0.038 (3)*
H9B	0.7566 (11)	0.2191 (14)	0.1471 (11)	0.036 (3)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N2	0.0360 (5)	0.0363 (5)	0.0385 (6)	0.0006 (4)	0.0077 (4)	0.0042 (4)
N1	0.0366 (5)	0.0373 (5)	0.0306 (5)	0.0046 (4)	0.0074 (4)	−0.0023 (4)
C7	0.0285 (5)	0.0345 (6)	0.0319 (6)	−0.0018 (4)	0.0082 (4)	−0.0003 (4)
O2	0.0613 (6)	0.0656 (7)	0.0290 (5)	−0.0100 (5)	0.0018 (4)	0.0040 (4)
C10	0.0420 (7)	0.0404 (7)	0.0440 (7)	0.0003 (5)	0.0135 (6)	−0.0044 (5)
O3	0.0414 (5)	0.0612 (6)	0.0685 (7)	−0.0114 (4)	0.0150 (5)	−0.0142 (5)
O1	0.0671 (7)	0.0587 (6)	0.0452 (6)	0.0075 (5)	0.0125 (5)	−0.0178 (5)
C6	0.0385 (6)	0.0456 (7)	0.0302 (6)	0.0014 (5)	0.0073 (5)	−0.0019 (5)
C8	0.0316 (6)	0.0402 (6)	0.0322 (6)	−0.0026 (5)	0.0072 (5)	0.0032 (5)
C2	0.0352 (6)	0.0475 (7)	0.0304 (6)	−0.0072 (5)	0.0058 (5)	0.0025 (5)
C9	0.0361 (6)	0.0362 (6)	0.0403 (7)	−0.0010 (5)	0.0086 (5)	0.0055 (5)
C5	0.0474 (8)	0.0460 (7)	0.0458 (8)	0.0010 (6)	0.0146 (6)	−0.0114 (6)
C1	0.0384 (6)	0.0449 (7)	0.0331 (6)	−0.0028 (5)	0.0089 (5)	−0.0053 (5)
C3	0.0423 (7)	0.0432 (7)	0.0474 (8)	0.0050 (5)	0.0074 (6)	0.0115 (6)
C13	0.0416 (7)	0.0487 (7)	0.0409 (7)	0.0013 (6)	0.0092 (6)	−0.0057 (6)
C4	0.0488 (8)	0.0391 (7)	0.0623 (9)	0.0076 (6)	0.0145 (7)	−0.0014 (6)
C12	0.0440 (7)	0.0652 (9)	0.0509 (9)	−0.0030 (7)	0.0033 (7)	−0.0131 (7)
C11	0.0405 (7)	0.0549 (8)	0.0611 (9)	−0.0008 (6)	0.0157 (7)	−0.0116 (7)

Geometric parameters (Å, º) top

N2—C9	1.4460 (16)	C8—C3	1.3850 (17)
N2—C13	1.4596 (16)	C8—C2	1.4597 (17)
N2—C10	1.4631 (16)	C2—C1	1.5490 (18)
N1—C1	1.3618 (15)	C9—H9A	1.024 (14)
N1—C7	1.4199 (14)	C9—H9B	0.979 (14)
N1—C9	1.4736 (15)	C5—C4	1.382 (2)
C7—C6	1.3765 (16)	C5—H5A	0.9300
C7—C8	1.4000 (15)	C3—C4	1.383 (2)
O2—C2	1.2075 (15)	C3—H3A	0.9300
C10—C11	1.5110 (18)	C13—C12	1.5109 (18)
C10—H10A	0.9700	C13—H13A	0.9700
C10—H10B	0.9700	C13—H13B	0.9700
O3—C11	1.4168 (16)	C4—H4A	0.9300
O3—C12	1.4217 (17)	C12—H12A	0.9700
O1—C1	1.2180 (14)	C12—H12B	0.9700
C6—C5	1.3914 (17)	C11—H11A	0.9700
C6—H6A	0.9300	C11—H11B	0.9700

C9—N2—C13	114.36 (10)	C4—C5—C6	121.82 (12)
C9—N2—C10	113.97 (10)	C4—C5—H5A	119.1
C13—N2—C10	109.92 (10)	C6—C5—H5A	119.1
C1—N1—C7	110.17 (10)	O1—C1—N1	126.89 (12)
C1—N1—C9	122.94 (10)	O1—C1—C2	126.25 (12)
C7—N1—C9	126.73 (10)	N1—C1—C2	106.86 (10)
C6—C7—C8	121.37 (11)	C4—C3—C8	118.27 (12)
C6—C7—N1	127.92 (11)	C4—C3—H3A	120.9
C8—C7—N1	110.71 (10)	C8—C3—H3A	120.9
N2—C10—C11	109.34 (11)	N2—C13—C12	109.35 (11)
N2—C10—H10A	109.8	N2—C13—H13A	109.8
C11—C10—H10A	109.8	C12—C13—H13A	109.8
N2—C10—H10B	109.8	N2—C13—H13B	109.8
C11—C10—H10B	109.8	C12—C13—H13B	109.8
H10A—C10—H10B	108.3	H13A—C13—H13B	108.3
C11—O3—C12	109.81 (11)	C3—C4—C5	120.66 (13)
C7—C6—C5	117.28 (11)	C3—C4—H4A	119.7
C7—C6—H6A	121.4	C5—C4—H4A	119.7
C5—C6—H6A	121.4	O3—C12—C13	111.11 (12)
C3—C8—C7	120.55 (11)	O3—C12—H12A	109.4
C3—C8—C2	132.02 (11)	C13—C12—H12A	109.4
C7—C8—C2	107.44 (10)	O3—C12—H12B	109.4
O2—C2—C8	131.85 (13)	C13—C12—H12B	109.4
O2—C2—C1	123.32 (12)	H12A—C12—H12B	108.0
C8—C2—C1	104.82 (10)	O3—C11—C10	111.53 (11)
N2—C9—N1	116.55 (10)	O3—C11—H11A	109.3
N2—C9—H9A	110.1 (7)	C10—C11—H11A	109.3
N1—C9—H9A	102.5 (7)	O3—C11—H11B	109.3
N2—C9—H9B	108.9 (7)	C10—C11—H11B	109.3
N1—C9—H9B	106.9 (7)	H11A—C11—H11B	108.0
H9A—C9—H9B	111.9 (10)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C6—H6A···O1ⁱ	0.93	2.47	3.349 (2)	158
C5—H5A···O2ⁱⁱ	0.93	2.52	3.216 (2)	131

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

Experimental details

Crystal data
Chemical formula	C₁₃H₁₄N₂O₃
M_r	246.26
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	293
a, b, c (Å)	11.608 (2), 8.2818 (17), 12.595 (3)
β (°)	100.20 (3)
V (Å³)	1191.7 (4)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.10
Crystal size (mm)	0.26 × 0.18 × 0.16

Data collection
Diffractometer	Bruker SMART CCD diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2001)
T_min, T_max	0.979, 0.984
No. of measured, independent and observed [I > 2σ(I)] reflections	7614, 3556, 2275
R_int	0.021
(sin θ/λ)_max (Å⁻¹)	0.712

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.042, 0.144, 0.99
No. of reflections	3556
No. of parameters	171
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.19, −0.22

Computer programs: SMART (Bruker, 2001), SAINT-Plus (Bruker, 2001), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C6—H6A···O1ⁱ	0.93	2.47	3.349 (2)	158
C5—H5A···O2ⁱⁱ	0.93	2.52	3.216 (2)	131

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

Acknowledgements

This work was supported financially by two grants from the National Science Foundation of China (No. 50874092) and the Natural Science Research Plan Projects of Shaanxi Science and Technology Department (SJ08B20).

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