organic compounds
1-{[3-(Thiophen-2-yl)-4,5-dihydro-1,2-oxazol-5-yl]methyl}-2,3-dihydro-1H-indole-2,3-dione
aLaboratoire de Chimie Organique Hétérocyclique, URAC 21, Pôle de Compétence Pharmacochimie, Av Ibn Battouta, BP 1014, Faculté des Sciences, Mohammed V University, Rabat, Morocco, and bDepartment of Chemistry, Tulane University, New Orleans, LA 70118, USA
*Correspondence e-mail: irayni@yahoo.fr
In the title compound, C16H12N2O3S, the indoline and thiophene rings are inclined to one another by 2.01 (2)°. The isoxazole ring adopts an with the methine C atom as the flap, and its mean plane is inclined to the thiophene and indoline ring mean planes by 19.78 (14) and 20.83 (12)°, respectively. In the crystal, molecules are linked by C—H⋯O hydrogen bonds involving the same acceptor atom, forming chains propagating along [010]. The chains are linked by further C—H⋯O hydrogen bonds, forming slabs parallel to the (-103) plane. The slabs are linked by offset π–π interactions [intercentroid distance = 3.792 (1) Å], forming a three-dimensional supramolecular structure.
Keywords: crystal structure; indoline; isoxazole; thiophene; hydrogen bonding; offset π–π interactions.
CCDC reference: 1534733
Structure description
Isatin (indoline-2,3-dione) is a core constituent of many et al., 2010), as well as dyes, pesticides and analytical reagents. Literature surveys reveal that various derivatives of isatin possess diverse biological activities, such as antibacterial, antifungal, antiviral, anti-HIV (Bal et al., 2005), anti-microbacterial, anticancer (Gürsoy & Karalı, 2003), anti-inflammatory (Sridhar & Ramesh, 2001) and anticonvulsant activities (Verma et al., 2004). Continuing our research on the synthesis of new heterocyclic systems containing isatin and other moieties (Alsubari et al., 2009; Bouhfid et al., 2006), we report herein on the synthesis and of the title compound, Fig. 1.
and drugs (Aboul-FadlIn the title compound, the indole ring system is almost planar as expected (r.m.s. deviation = 0.023 Å). The dihedral angle between this plane and that of the thiophene ring (r.m.s. deviation = 0.012 Å) is 2.01 (2)°. Puckering analysis of the isoxazole ring [parameters Q(2) = 0.175 (2) Å and φ(2) = 326.2 (8)°], indicates that it has an with atom C10 as the flap. Its mean plane is inclined to the thiophene and indoline ring mean planes by 19.78 (14) and 20.83 (12)°, respectively.
In the crystal, the combination of C2—H2⋯O2i, C9—H9A⋯O2i and C16—H16⋯O1ii hydrogen bonds (Table 1) forms stepped layers, or slabs two molecules thick, which are oriented parallel to (03); as shown in Fig. 2. These layers are associated through offset π-stacking interactions, involving inversion-related indole rings in adjacent layers, forming a supramolecular three-dimensional structure [Cg⋯Cgiii = 3.792 (1) Å, Cg is the centroid of the N1/C1–C8 ring, interplanar distance = 3.479 (1) Å, slippage = 1.508 Å, symmetry code (iii): −x + 2, −y + 1, −z + 1].
Synthesis and crystallization
To a solution of 0.4 g (2.18 mmol) of 1-allylindoline-2,3-dione and 0.5 g (4 mmol) of 2-thiophenecarboxaldehyde oxime in 15 ml of chloroform, were added 15 ml of bleach (24% weight) with a dropping funnel. The mixture was stirred for 4 h at 273 K. The solution was then concentrated to dryness under reduced pressure and the residue extracted with chloroform. The product isolated was chromatographed on a silica column (eluent: hexane/ethyl acetate 95:5 v/v). The solid obtained was crystallized from ethanol solution to give colourless rod-like crystals of the title compound.
Refinement
Crystal data, data collection and structure .
details are summarized in Table 2Structural data
CCDC reference: 1534733
https://doi.org/10.1107/S2414314617003157/su4133sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314617003157/su4133Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2414314617003157/su4133Isup3.cdx
Supporting information file. DOI: https://doi.org/10.1107/S2414314617003157/su4133Isup4.cml
Data collection: APEX3 (Bruker, 2016); cell
SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: DIAMOND (Brandenburg & Putz, 2012); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).C16H12N2O3S | F(000) = 648 |
Mr = 312.34 | Dx = 1.446 Mg m−3 |
Monoclinic, P21/n | Cu Kα radiation, λ = 1.54178 Å |
a = 7.3834 (2) Å | Cell parameters from 8282 reflections |
b = 11.7331 (3) Å | θ = 3.8–74.3° |
c = 16.9144 (4) Å | µ = 2.14 mm−1 |
β = 101.731 (1)° | T = 298 K |
V = 1434.69 (6) Å3 | Rod, colourless |
Z = 4 | 0.24 × 0.19 × 0.14 mm |
Bruker D8 VENTURE PHOTON 100 CMOS diffractometer | 2899 independent reflections |
Radiation source: INCOATEC IµS micro-focus source | 2500 reflections with I > 2σ(I) |
Mirror monochromator | Rint = 0.031 |
Detector resolution: 10.4167 pixels mm-1 | θmax = 74.7°, θmin = 4.6° |
ω scans | h = −9→9 |
Absorption correction: multi-scan (SADABS; Bruker, 2016) | k = −14→14 |
Tmin = 0.64, Tmax = 0.76 | l = −18→20 |
10930 measured reflections |
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)] = 0.057 | Hydrogen site location: mixed |
wR(F2) = 0.166 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.06 | w = 1/[σ2(Fo2) + (0.089P)2 + 0.7078P] where P = (Fo2 + 2Fc2)/3 |
2899 reflections | (Δ/σ)max < 0.001 |
235 parameters | Δρmax = 0.80 e Å−3 |
0 restraints | Δρmin = −0.38 e Å−3 |
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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. The H-atoms of the thiophene moiety, although located in a difference map, did not refine satisfactorily and so were included as riding contributions in idealized positions. |
x | y | z | Uiso*/Ueq | ||
S1 | −0.04891 (11) | 0.36107 (6) | 0.11798 (5) | 0.0697 (3) | |
O1 | 1.1460 (3) | 0.26341 (19) | 0.43119 (14) | 0.0835 (7) | |
O2 | 0.8130 (3) | 0.26371 (15) | 0.30166 (14) | 0.0718 (5) | |
O3 | 0.4468 (2) | 0.41608 (18) | 0.32154 (12) | 0.0679 (6) | |
N1 | 0.8448 (2) | 0.45816 (15) | 0.31846 (11) | 0.0434 (4) | |
N2 | 0.2829 (3) | 0.39068 (19) | 0.26398 (14) | 0.0600 (6) | |
C1 | 0.9740 (3) | 0.53126 (18) | 0.36675 (12) | 0.0410 (5) | |
C2 | 0.9783 (3) | 0.6487 (2) | 0.36514 (16) | 0.0526 (6) | |
H2 | 0.900 (4) | 0.691 (2) | 0.3307 (18) | 0.063 (8)* | |
C3 | 1.1224 (4) | 0.7019 (3) | 0.41754 (19) | 0.0687 (8) | |
H3 | 1.130 (5) | 0.778 (3) | 0.415 (2) | 0.081 (10)* | |
C4 | 1.2542 (4) | 0.6412 (3) | 0.47017 (19) | 0.0729 (8) | |
H4 | 1.347 (5) | 0.685 (3) | 0.508 (2) | 0.082 (10)* | |
C5 | 1.2494 (3) | 0.5240 (3) | 0.47092 (16) | 0.0640 (7) | |
H5 | 1.332 (5) | 0.486 (3) | 0.506 (2) | 0.083 (10)* | |
C6 | 1.1086 (3) | 0.4687 (2) | 0.41850 (13) | 0.0486 (5) | |
C7 | 1.0666 (4) | 0.3480 (2) | 0.40177 (16) | 0.0560 (6) | |
C8 | 0.8915 (3) | 0.34648 (19) | 0.33422 (15) | 0.0509 (5) | |
C9 | 0.6847 (3) | 0.4973 (2) | 0.26000 (13) | 0.0445 (5) | |
H9A | 0.715 (3) | 0.566 (2) | 0.2327 (15) | 0.048 (6)* | |
H9B | 0.656 (4) | 0.439 (2) | 0.2200 (16) | 0.053 (7)* | |
C10 | 0.5214 (3) | 0.5228 (2) | 0.29834 (16) | 0.0525 (6) | |
H10 | 0.550 (4) | 0.557 (3) | 0.3435 (18) | 0.062 (8)* | |
C11 | 0.3615 (3) | 0.5784 (2) | 0.24054 (18) | 0.0553 (6) | |
H11A | 0.299 (5) | 0.641 (3) | 0.267 (2) | 0.102 (12)* | |
H11B | 0.403 (4) | 0.607 (3) | 0.1921 (19) | 0.071 (8)* | |
C12 | 0.2347 (3) | 0.47894 (19) | 0.22011 (14) | 0.0464 (5) | |
C13 | 0.0679 (3) | 0.4814 (2) | 0.15739 (14) | 0.0492 (5) | |
C14 | −0.0204 (3) | 0.5768 (2) | 0.12228 (15) | 0.0567 (6) | |
H14 | 0.0221 | 0.6506 | 0.1345 | 0.068* | |
C15 | −0.1833 (5) | 0.5507 (3) | 0.06558 (19) | 0.0782 (9) | |
H15 | −0.2618 | 0.6058 | 0.0376 | 0.094* | |
C16 | −0.2132 (5) | 0.4392 (3) | 0.05624 (18) | 0.0768 (8) | |
H16 | −0.3124 | 0.4078 | 0.0201 | 0.092* |
U11 | U22 | U33 | U12 | U13 | U23 | |
S1 | 0.0667 (5) | 0.0567 (4) | 0.0878 (5) | −0.0080 (3) | 0.0209 (4) | −0.0166 (3) |
O1 | 0.0917 (15) | 0.0672 (12) | 0.0930 (15) | 0.0322 (11) | 0.0222 (12) | 0.0312 (11) |
O2 | 0.0805 (13) | 0.0373 (9) | 0.0984 (14) | −0.0077 (9) | 0.0201 (11) | −0.0075 (9) |
O3 | 0.0485 (9) | 0.0835 (13) | 0.0735 (12) | 0.0074 (9) | 0.0166 (8) | 0.0340 (10) |
N1 | 0.0412 (9) | 0.0336 (9) | 0.0540 (10) | −0.0005 (7) | 0.0063 (8) | −0.0014 (7) |
N2 | 0.0500 (11) | 0.0611 (12) | 0.0718 (13) | −0.0004 (9) | 0.0190 (10) | 0.0190 (10) |
C1 | 0.0357 (9) | 0.0419 (11) | 0.0455 (11) | −0.0003 (8) | 0.0087 (8) | −0.0038 (8) |
C2 | 0.0526 (13) | 0.0418 (12) | 0.0615 (14) | −0.0012 (10) | 0.0069 (11) | −0.0051 (10) |
C3 | 0.0675 (17) | 0.0587 (17) | 0.0792 (18) | −0.0155 (13) | 0.0131 (14) | −0.0221 (14) |
C4 | 0.0537 (15) | 0.095 (2) | 0.0673 (17) | −0.0160 (15) | 0.0061 (13) | −0.0243 (16) |
C5 | 0.0410 (12) | 0.096 (2) | 0.0536 (14) | 0.0060 (13) | 0.0068 (10) | 0.0028 (13) |
C6 | 0.0397 (10) | 0.0608 (14) | 0.0466 (11) | 0.0073 (9) | 0.0119 (9) | 0.0049 (10) |
C7 | 0.0562 (13) | 0.0540 (13) | 0.0617 (14) | 0.0152 (11) | 0.0213 (11) | 0.0148 (11) |
C8 | 0.0543 (13) | 0.0379 (11) | 0.0640 (14) | 0.0028 (9) | 0.0204 (11) | 0.0035 (10) |
C9 | 0.0407 (10) | 0.0453 (11) | 0.0463 (11) | −0.0025 (9) | 0.0060 (9) | −0.0013 (9) |
C10 | 0.0458 (12) | 0.0581 (14) | 0.0528 (13) | 0.0034 (10) | 0.0078 (10) | −0.0025 (11) |
C11 | 0.0437 (11) | 0.0466 (13) | 0.0729 (16) | 0.0028 (10) | 0.0053 (11) | 0.0018 (11) |
C12 | 0.0435 (11) | 0.0455 (11) | 0.0539 (12) | 0.0016 (9) | 0.0186 (9) | 0.0027 (9) |
C13 | 0.0490 (12) | 0.0504 (12) | 0.0506 (12) | −0.0040 (10) | 0.0159 (10) | −0.0014 (9) |
C14 | 0.0562 (13) | 0.0495 (13) | 0.0605 (14) | −0.0050 (10) | 0.0025 (11) | 0.0108 (10) |
C15 | 0.0731 (18) | 0.089 (2) | 0.0645 (17) | −0.0021 (16) | −0.0043 (14) | 0.0148 (15) |
C16 | 0.0726 (18) | 0.094 (2) | 0.0610 (16) | −0.0175 (17) | 0.0073 (13) | −0.0166 (15) |
S1—C16 | 1.699 (4) | C5—H5 | 0.88 (4) |
S1—C13 | 1.717 (2) | C6—C7 | 1.465 (4) |
O1—C7 | 1.207 (3) | C7—C8 | 1.542 (4) |
O2—C8 | 1.205 (3) | C9—C10 | 1.510 (3) |
O3—N2 | 1.422 (3) | C9—H9A | 0.98 (3) |
O3—C10 | 1.454 (3) | C9—H9B | 0.96 (3) |
N1—C8 | 1.367 (3) | C10—C11 | 1.519 (3) |
N1—C1 | 1.413 (3) | C10—H10 | 0.85 (3) |
N1—C9 | 1.453 (3) | C11—C12 | 1.493 (3) |
N2—C12 | 1.282 (3) | C11—H11A | 1.02 (4) |
C1—C2 | 1.379 (3) | C11—H11B | 0.99 (3) |
C1—C6 | 1.393 (3) | C12—C13 | 1.453 (3) |
C2—C3 | 1.387 (4) | C13—C14 | 1.369 (3) |
C2—H2 | 0.88 (3) | C14—C15 | 1.411 (4) |
C3—C4 | 1.376 (5) | C14—H14 | 0.9300 |
C3—H3 | 0.89 (4) | C15—C16 | 1.331 (5) |
C4—C5 | 1.376 (5) | C15—H15 | 0.9300 |
C4—H4 | 0.98 (3) | C16—H16 | 0.9300 |
C5—C6 | 1.384 (4) | ||
C16—S1—C13 | 91.96 (14) | C10—C9—H9A | 108.8 (14) |
N2—O3—C10 | 108.19 (17) | N1—C9—H9B | 106.8 (16) |
C8—N1—C1 | 110.79 (18) | C10—C9—H9B | 111.4 (15) |
C8—N1—C9 | 125.00 (19) | H9A—C9—H9B | 107 (2) |
C1—N1—C9 | 124.21 (18) | O3—C10—C9 | 108.9 (2) |
C12—N2—O3 | 109.0 (2) | O3—C10—C11 | 104.84 (19) |
C2—C1—C6 | 121.5 (2) | C9—C10—C11 | 113.1 (2) |
C2—C1—N1 | 127.7 (2) | O3—C10—H10 | 102 (2) |
C6—C1—N1 | 110.8 (2) | C9—C10—H10 | 114 (2) |
C1—C2—C3 | 117.0 (3) | C11—C10—H10 | 113 (2) |
C1—C2—H2 | 123.7 (19) | C12—C11—C10 | 100.50 (19) |
C3—C2—H2 | 119.1 (19) | C12—C11—H11A | 110 (2) |
C4—C3—C2 | 122.1 (3) | C10—C11—H11A | 113 (2) |
C4—C3—H3 | 121 (2) | C12—C11—H11B | 111.0 (18) |
C2—C3—H3 | 117 (2) | C10—C11—H11B | 110.4 (18) |
C5—C4—C3 | 120.4 (3) | H11A—C11—H11B | 112 (3) |
C5—C4—H4 | 122.0 (19) | N2—C12—C13 | 122.2 (2) |
C3—C4—H4 | 117.5 (19) | N2—C12—C11 | 114.2 (2) |
C4—C5—C6 | 118.7 (3) | C13—C12—C11 | 123.5 (2) |
C4—C5—H5 | 120 (2) | C14—C13—C12 | 126.3 (2) |
C6—C5—H5 | 121 (2) | C14—C13—S1 | 110.26 (19) |
C5—C6—C1 | 120.2 (2) | C12—C13—S1 | 123.45 (18) |
C5—C6—C7 | 132.8 (2) | C13—C14—C15 | 112.5 (3) |
C1—C6—C7 | 107.0 (2) | C13—C14—H14 | 123.7 |
O1—C7—C6 | 130.5 (3) | C15—C14—H14 | 123.7 |
O1—C7—C8 | 124.1 (3) | C16—C15—C14 | 113.0 (3) |
C6—C7—C8 | 105.47 (18) | C16—C15—H15 | 123.5 |
O2—C8—N1 | 127.2 (2) | C14—C15—H15 | 123.5 |
O2—C8—C7 | 126.9 (2) | C15—C16—S1 | 112.2 (2) |
N1—C8—C7 | 105.9 (2) | C15—C16—H16 | 123.9 |
N1—C9—C10 | 112.35 (19) | S1—C16—H16 | 123.9 |
N1—C9—H9A | 110.3 (14) | ||
C10—O3—N2—C12 | −12.4 (3) | O1—C7—C8—N1 | 179.6 (2) |
C8—N1—C1—C2 | 176.5 (2) | C6—C7—C8—N1 | −1.1 (2) |
C9—N1—C1—C2 | −3.3 (3) | C8—N1—C9—C10 | 96.1 (3) |
C8—N1—C1—C6 | −2.0 (2) | C1—N1—C9—C10 | −84.1 (3) |
C9—N1—C1—C6 | 178.19 (19) | N2—O3—C10—C9 | −103.2 (2) |
C6—C1—C2—C3 | −0.2 (4) | N2—O3—C10—C11 | 18.1 (3) |
N1—C1—C2—C3 | −178.6 (2) | N1—C9—C10—O3 | −71.4 (2) |
C1—C2—C3—C4 | −1.2 (4) | N1—C9—C10—C11 | 172.41 (19) |
C2—C3—C4—C5 | 1.7 (5) | O3—C10—C11—C12 | −16.3 (2) |
C3—C4—C5—C6 | −0.7 (4) | C9—C10—C11—C12 | 102.3 (2) |
C4—C5—C6—C1 | −0.6 (4) | O3—N2—C12—C13 | −177.69 (19) |
C4—C5—C6—C7 | 177.5 (3) | O3—N2—C12—C11 | 0.9 (3) |
C2—C1—C6—C5 | 1.1 (3) | C10—C11—C12—N2 | 10.0 (3) |
N1—C1—C6—C5 | 179.7 (2) | C10—C11—C12—C13 | −171.4 (2) |
C2—C1—C6—C7 | −177.5 (2) | N2—C12—C13—C14 | 161.9 (2) |
N1—C1—C6—C7 | 1.2 (2) | C11—C12—C13—C14 | −16.6 (4) |
C5—C6—C7—O1 | 1.0 (5) | N2—C12—C13—S1 | −16.9 (3) |
C1—C6—C7—O1 | 179.2 (3) | C11—C12—C13—S1 | 164.62 (19) |
C5—C6—C7—C8 | −178.3 (2) | C16—S1—C13—C14 | −0.3 (2) |
C1—C6—C7—C8 | −0.1 (2) | C16—S1—C13—C12 | 178.6 (2) |
C1—N1—C8—O2 | −177.7 (2) | C12—C13—C14—C15 | −177.5 (2) |
C9—N1—C8—O2 | 2.1 (4) | S1—C13—C14—C15 | 1.4 (3) |
C1—N1—C8—C7 | 1.8 (2) | C13—C14—C15—C16 | −2.1 (4) |
C9—N1—C8—C7 | −178.35 (18) | C14—C15—C16—S1 | 1.9 (4) |
O1—C7—C8—O2 | −0.9 (4) | C13—S1—C16—C15 | −0.9 (3) |
C6—C7—C8—O2 | 178.4 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
C2—H2···O2i | 0.88 (3) | 2.60 (3) | 3.455 (3) | 162 (2) |
C9—H9A···O2i | 0.98 (3) | 2.39 (3) | 3.297 (3) | 153.7 (19) |
C16—H16···O1ii | 0.93 | 2.49 | 3.212 (4) | 134 |
Symmetry codes: (i) −x+3/2, y+1/2, −z+1/2; (ii) x−3/2, −y+1/2, z−1/2. |
Acknowledgements
The support of NSF–MRI Grant No.1228232 for the purchase of the diffractometer and Tulane University for support of the Tulane Crystallography Laboratory are gratefully acknowledged.
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