organic compounds
4-[(3-Phenyl-4,5-dihydroisoxazol-5-yl)methyl]-2H-benzo[b][1,4]thiazin-3(4H)-one
aLaboratoire de Chimie Organique Hétérocyclique URAC 21, Pôle de Compétences Pharmacochimie, Mohammed V University in Rabat, BP 1014 Avenue Ibn Batouta, Rabat, Morocco, and bLaboratoire de Chimie du Solide Appliquée, Faculty of Sciences, Mohammed V University in Rabat, Avenue Ibn Battouta, BP 1014, Rabat, Morocco
*Correspondence e-mail: nk_sebbar@yahoo.fr
In the title compound, C18H16N2O2S, the 5-dihydroisoxazol-5-yl ring and its phenyl substituent are nearly coplanar, with the largest deviation from the mean plane being 0.0184 (16) Å. The thiomorpholin-3-one ring adopts a screw-boat conformation and the attached benzene ring makes a dihedral angle of 42.26 (7)° with the mean plane through the 3-phenyl-4,5-dihydroisoxazol-5-yl ring system. In the crystal, molecules are linked by pairs of C—H⋯N hydrogen bonds, forming inversion dimers. These dimers are linked via C—H⋯O hydrogen bonds, generating a three-dimensional network.
CCDC reference: 1486932
Structure description
1,4-Benzothiazines are a class of medicinally important et al., 1996). They can also act as calcium channel blockers (Schwarz et al., 1999), phosphodiesterase-7 inhibitors (Castro et al., 2001) and anticataract agents (Kawashima et al., 1994). Isoxazole derivatives represent a unique class of nitrogen- and oxygen-containing five-membered heterocycles. They are the components of a variety of natural products and medicinally useful compounds (Sperry et al., 2005). Isoxazole derivatives with a variety of substituents are known to have various biological activities in both the pharmaceutical and agricultural areas (Lang & Lin, 1984; Boyd, 1991).
which are used extensively in drug design. It is well documented that 1,4-benzothiazin-3-one derivatives possess important pharmacological properties and play a vital role in the treatment of neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease (ShenThe present work is a continuation of our investigations of new derivatives of 2H-benzo[b][1,4]thiazin-3(4H)-one for their biological activities (Sebbar et al., 2014a,b). The nitrile oxide, formed in situ by chlorination of an oxime, reacts with 4-allyl-2H-benzo[b][1,4]thiazin-3(4H)-one in a biphasic medium (water–chloroform) at 0°C over 4 h to afford the unique cycloadduct 4-((3-phenyl-4,5-dihydroisoxazol-5-yl)methyl)-2H-benzo[b] [1,4]thiazin-3(4H)-one.
The molecule of the title compound contains the two fused six-membered rings of the 1,4-benzothiazine unit, linked, through a methylene group, to the 3-phenyl-4,5-dihydroisoxazol-5-yl ring system, as shown in Fig. 1. The dihydroisoxazole and phenyl rings are almost coplanar, as indicated by the dihedral angle of 1.33 (9)° between their planes. The six-membered heterocycle adopts a screw-boat conformation, as indicated by the total puckering amplitude QT = 0.6390 (2) Å, and a spherical polar angle θ = 65.02 (1)° with φ = 326.38 (2)°. The dihedral angle between the phenyl (C13–C18) and the benzene (C1–C6) rings is 42.42 (9)°. An intramolecular C5—H5⋯O2 interaction closes a seven-membered ring.
In the crystal, C10—H10⋯N2 hydrogen bonds form inversion dimers, generating R22(8) rings. These dimers are further connected by C2—H2⋯O1 hydrogen bonds, forming a three-dimensional network, Fig. 2 and Table 1.
Synthesis and crystallization
A 24% sodium hypochlorite solution (10 ml) was added dropwise to a solution of 4-allyl-2H-benzo[b][1,4]thiazin-3(4H)-one (0.5 g, 2.4 mmol) and benzaldoxime (0.52 ml, 4.8 mmol) in chloroform (30 ml) at 0°C. Stirring was continued for 4 h. The organic layer was dried over Na2SO4 and the solvent was evaporated under reduced pressure. The residue was then purified by on silica gel using a mixture of hexane/ethyl acetate (v/v = 90/10) as Colourless crystals were isolated when the solvent was allowed to evaporate (yield = 38%, m.p. = 408 K).
Refinement
Crystal data, data collection and structure .
details are summarized in Table 2Structural data
CCDC reference: 1486932
10.1107/S2414314616010129/sj4050sup1.cif
contains datablock I. DOI:Structure factors: contains datablock I. DOI: 10.1107/S2414314616010129/sj4050Isup2.hkl
Supporting information file. DOI: 10.1107/S2414314616010129/sj4050Isup3.cml
Data collection: APEX2 (Bruker, 2009); cell
SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: ORTEPIII (Burnett & Johnson, 1996), ORTEP-3 for Windows (Farrugia, 2012) and Mercury (Macrae et al., 2008); software used to prepare material for publication: PLATON (Spek, 2009) and publCIF (Westrip, 2010).C18H16N2O2S | Dx = 1.378 Mg m−3 |
Mr = 324.39 | Mo Kα radiation, λ = 0.71073 Å |
Orthorhombic, Pbca | Cell parameters from 4391 reflections |
a = 11.7526 (3) Å | θ = 2.7–29.6° |
b = 10.4082 (3) Å | µ = 0.22 mm−1 |
c = 25.5656 (7) Å | T = 296 K |
V = 3127.27 (15) Å3 | Block, colourless |
Z = 8 | 0.35 × 0.31 × 0.22 mm |
F(000) = 1360 |
Bruker X8 APEX diffractometer | 4391 independent reflections |
Radiation source: fine-focus sealed tube | 2776 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.049 |
φ and ω scans | θmax = 29.6°, θmin = 2.7° |
Absorption correction: multi-scan (SADABS; Bruker, 2009) | h = −16→16 |
Tmin = 0.626, Tmax = 0.746 | k = −14→14 |
41764 measured reflections | l = −35→35 |
Refinement on F2 | 0 restraints |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.042 | H-atom parameters constrained |
wR(F2) = 0.116 | w = 1/[σ2(Fo2) + (0.0471P)2 + 0.5946P] where P = (Fo2 + 2Fc2)/3 |
S = 1.02 | (Δ/σ)max = 0.001 |
4391 reflections | Δρmax = 0.18 e Å−3 |
208 parameters | Δρmin = −0.23 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. |
x | y | z | Uiso*/Ueq | ||
C1 | 0.41617 (14) | 0.54751 (16) | 0.72451 (6) | 0.0523 (4) | |
C2 | 0.31872 (17) | 0.5156 (2) | 0.75261 (7) | 0.0697 (5) | |
H2 | 0.3001 | 0.5621 | 0.7825 | 0.084* | |
C3 | 0.25022 (17) | 0.4171 (2) | 0.73689 (9) | 0.0753 (6) | |
H3 | 0.1870 | 0.3942 | 0.7567 | 0.090* | |
C4 | 0.27550 (15) | 0.3520 (2) | 0.69163 (9) | 0.0702 (5) | |
H4 | 0.2286 | 0.2853 | 0.6806 | 0.084* | |
C5 | 0.37013 (13) | 0.38471 (16) | 0.66217 (7) | 0.0542 (4) | |
H5 | 0.3846 | 0.3418 | 0.6309 | 0.065* | |
C6 | 0.44335 (11) | 0.48065 (14) | 0.67880 (6) | 0.0435 (3) | |
C7 | 0.60226 (13) | 0.62130 (15) | 0.65330 (6) | 0.0497 (4) | |
C8 | 0.54562 (16) | 0.72680 (17) | 0.68349 (8) | 0.0663 (5) | |
H8A | 0.4789 | 0.7563 | 0.6646 | 0.080* | |
H8B | 0.5975 | 0.7987 | 0.6870 | 0.080* | |
C9 | 0.60129 (13) | 0.40421 (14) | 0.62058 (6) | 0.0459 (3) | |
H9A | 0.5695 | 0.3220 | 0.6309 | 0.055* | |
H9B | 0.6818 | 0.4029 | 0.6288 | 0.055* | |
C10 | 0.58705 (13) | 0.42034 (16) | 0.56196 (6) | 0.0521 (4) | |
H10 | 0.6170 | 0.5042 | 0.5512 | 0.062* | |
C11 | 0.64431 (13) | 0.31506 (18) | 0.53054 (6) | 0.0569 (4) | |
H11A | 0.7005 | 0.3499 | 0.5066 | 0.068* | |
H11B | 0.6803 | 0.2522 | 0.5531 | 0.068* | |
C12 | 0.54543 (12) | 0.25839 (15) | 0.50168 (6) | 0.0455 (3) | |
C13 | 0.55384 (12) | 0.15192 (14) | 0.46429 (6) | 0.0459 (3) | |
C14 | 0.65787 (14) | 0.09460 (18) | 0.45405 (7) | 0.0585 (4) | |
H14 | 0.7230 | 0.1232 | 0.4711 | 0.070* | |
C15 | 0.66500 (17) | −0.00510 (19) | 0.41843 (8) | 0.0702 (5) | |
H15 | 0.7351 | −0.0431 | 0.4116 | 0.084* | |
C16 | 0.56970 (19) | −0.04828 (18) | 0.39314 (8) | 0.0720 (5) | |
H16 | 0.5754 | −0.1147 | 0.3689 | 0.086* | |
C17 | 0.46626 (18) | 0.00613 (19) | 0.40342 (8) | 0.0728 (5) | |
H17 | 0.4015 | −0.0241 | 0.3866 | 0.087* | |
C18 | 0.45782 (14) | 0.10545 (18) | 0.43862 (7) | 0.0601 (4) | |
H18 | 0.3871 | 0.1421 | 0.4454 | 0.072* | |
N1 | 0.54641 (10) | 0.50614 (11) | 0.65117 (5) | 0.0430 (3) | |
N2 | 0.45035 (11) | 0.31124 (14) | 0.51224 (5) | 0.0527 (3) | |
O1 | 0.69382 (10) | 0.63712 (12) | 0.63161 (5) | 0.0650 (3) | |
O2 | 0.46655 (10) | 0.41189 (12) | 0.54839 (4) | 0.0624 (3) | |
S1 | 0.50438 (4) | 0.67123 (5) | 0.74704 (2) | 0.07191 (17) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0519 (9) | 0.0552 (9) | 0.0497 (9) | 0.0146 (7) | 0.0002 (7) | 0.0048 (7) |
C2 | 0.0669 (11) | 0.0824 (13) | 0.0598 (11) | 0.0234 (11) | 0.0166 (9) | 0.0110 (10) |
C3 | 0.0579 (11) | 0.0884 (15) | 0.0797 (13) | 0.0079 (10) | 0.0217 (10) | 0.0245 (12) |
C4 | 0.0530 (10) | 0.0714 (12) | 0.0863 (14) | −0.0099 (9) | 0.0019 (9) | 0.0188 (11) |
C5 | 0.0497 (8) | 0.0538 (9) | 0.0592 (10) | −0.0013 (7) | 0.0002 (7) | 0.0063 (8) |
C6 | 0.0402 (7) | 0.0454 (8) | 0.0450 (8) | 0.0074 (6) | −0.0005 (6) | 0.0080 (6) |
C7 | 0.0438 (8) | 0.0533 (9) | 0.0522 (9) | −0.0016 (7) | −0.0074 (7) | 0.0031 (7) |
C8 | 0.0650 (11) | 0.0482 (9) | 0.0858 (13) | −0.0028 (8) | −0.0004 (10) | −0.0060 (9) |
C9 | 0.0453 (8) | 0.0498 (8) | 0.0425 (8) | 0.0068 (6) | −0.0022 (6) | 0.0007 (6) |
C10 | 0.0485 (8) | 0.0642 (10) | 0.0436 (8) | 0.0027 (7) | −0.0028 (7) | 0.0009 (7) |
C11 | 0.0413 (8) | 0.0835 (12) | 0.0459 (8) | 0.0013 (8) | −0.0003 (6) | −0.0087 (8) |
C12 | 0.0370 (7) | 0.0612 (9) | 0.0383 (7) | 0.0002 (7) | 0.0002 (6) | 0.0100 (7) |
C13 | 0.0440 (8) | 0.0540 (9) | 0.0399 (7) | −0.0026 (7) | 0.0017 (6) | 0.0103 (7) |
C14 | 0.0474 (9) | 0.0698 (11) | 0.0583 (10) | −0.0009 (8) | 0.0052 (7) | −0.0011 (9) |
C15 | 0.0731 (12) | 0.0669 (12) | 0.0707 (12) | 0.0076 (10) | 0.0157 (10) | 0.0000 (10) |
C16 | 0.0975 (16) | 0.0535 (10) | 0.0648 (12) | −0.0091 (10) | 0.0013 (11) | −0.0019 (9) |
C17 | 0.0792 (13) | 0.0665 (12) | 0.0727 (13) | −0.0157 (10) | −0.0147 (10) | 0.0011 (10) |
C18 | 0.0491 (9) | 0.0676 (11) | 0.0637 (11) | −0.0041 (8) | −0.0055 (8) | 0.0050 (9) |
N1 | 0.0405 (6) | 0.0449 (7) | 0.0437 (7) | 0.0028 (5) | −0.0012 (5) | 0.0003 (5) |
N2 | 0.0446 (7) | 0.0686 (9) | 0.0450 (7) | 0.0067 (6) | −0.0046 (6) | 0.0051 (6) |
O1 | 0.0485 (6) | 0.0717 (8) | 0.0748 (8) | −0.0112 (6) | 0.0023 (6) | 0.0029 (6) |
O2 | 0.0507 (6) | 0.0866 (9) | 0.0500 (6) | 0.0193 (6) | −0.0083 (5) | −0.0092 (6) |
S1 | 0.0788 (3) | 0.0722 (3) | 0.0647 (3) | 0.0081 (2) | −0.0025 (2) | −0.0221 (2) |
C1—C2 | 1.392 (2) | C9—H9B | 0.9700 |
C1—C6 | 1.397 (2) | C10—O2 | 1.4607 (19) |
C1—S1 | 1.7506 (18) | C10—C11 | 1.516 (2) |
C2—C3 | 1.364 (3) | C10—H10 | 0.9800 |
C2—H2 | 0.9300 | C11—C12 | 1.498 (2) |
C3—C4 | 1.373 (3) | C11—H11A | 0.9700 |
C3—H3 | 0.9300 | C11—H11B | 0.9700 |
C4—C5 | 1.386 (2) | C12—N2 | 1.2744 (19) |
C4—H4 | 0.9300 | C12—C13 | 1.467 (2) |
C5—C6 | 1.385 (2) | C13—C14 | 1.385 (2) |
C5—H5 | 0.9300 | C13—C18 | 1.392 (2) |
C6—N1 | 1.4271 (18) | C14—C15 | 1.383 (3) |
C7—O1 | 1.2217 (19) | C14—H14 | 0.9300 |
C7—N1 | 1.3677 (19) | C15—C16 | 1.369 (3) |
C7—C8 | 1.498 (2) | C15—H15 | 0.9300 |
C8—S1 | 1.792 (2) | C16—C17 | 1.367 (3) |
C8—H8A | 0.9700 | C16—H16 | 0.9300 |
C8—H8B | 0.9700 | C17—C18 | 1.374 (3) |
C9—N1 | 1.4673 (18) | C17—H17 | 0.9300 |
C9—C10 | 1.517 (2) | C18—H18 | 0.9300 |
C9—H9A | 0.9700 | N2—O2 | 1.4098 (18) |
C2—C1—C6 | 120.06 (17) | O2—C10—H10 | 109.6 |
C2—C1—S1 | 119.53 (14) | C11—C10—H10 | 109.6 |
C6—C1—S1 | 120.41 (13) | C9—C10—H10 | 109.6 |
C3—C2—C1 | 120.86 (19) | C12—C11—C10 | 101.61 (12) |
C3—C2—H2 | 119.6 | C12—C11—H11A | 111.4 |
C1—C2—H2 | 119.6 | C10—C11—H11A | 111.4 |
C2—C3—C4 | 119.42 (18) | C12—C11—H11B | 111.4 |
C2—C3—H3 | 120.3 | C10—C11—H11B | 111.4 |
C4—C3—H3 | 120.3 | H11A—C11—H11B | 109.3 |
C3—C4—C5 | 120.71 (19) | N2—C12—C13 | 121.56 (14) |
C3—C4—H4 | 119.6 | N2—C12—C11 | 113.95 (14) |
C5—C4—H4 | 119.6 | C13—C12—C11 | 124.49 (13) |
C6—C5—C4 | 120.58 (17) | C14—C13—C18 | 118.47 (16) |
C6—C5—H5 | 119.7 | C14—C13—C12 | 120.53 (14) |
C4—C5—H5 | 119.7 | C18—C13—C12 | 121.00 (14) |
C5—C6—C1 | 118.28 (14) | C15—C14—C13 | 120.06 (17) |
C5—C6—N1 | 120.62 (14) | C15—C14—H14 | 120.0 |
C1—C6—N1 | 121.03 (14) | C13—C14—H14 | 120.0 |
O1—C7—N1 | 121.51 (15) | C16—C15—C14 | 120.51 (18) |
O1—C7—C8 | 121.76 (15) | C16—C15—H15 | 119.7 |
N1—C7—C8 | 116.73 (14) | C14—C15—H15 | 119.7 |
C7—C8—S1 | 110.53 (12) | C17—C16—C15 | 120.05 (19) |
C7—C8—H8A | 109.5 | C17—C16—H16 | 120.0 |
S1—C8—H8A | 109.5 | C15—C16—H16 | 120.0 |
C7—C8—H8B | 109.5 | C16—C17—C18 | 120.13 (18) |
S1—C8—H8B | 109.5 | C16—C17—H17 | 119.9 |
H8A—C8—H8B | 108.1 | C18—C17—H17 | 119.9 |
N1—C9—C10 | 113.45 (12) | C17—C18—C13 | 120.77 (17) |
N1—C9—H9A | 108.9 | C17—C18—H18 | 119.6 |
C10—C9—H9A | 108.9 | C13—C18—H18 | 119.6 |
N1—C9—H9B | 108.9 | C7—N1—C6 | 123.40 (12) |
C10—C9—H9B | 108.9 | C7—N1—C9 | 116.36 (12) |
H9A—C9—H9B | 107.7 | C6—N1—C9 | 120.16 (12) |
O2—C10—C11 | 105.13 (12) | C12—N2—O2 | 109.95 (12) |
O2—C10—C9 | 109.56 (13) | N2—O2—C10 | 109.35 (11) |
C11—C10—C9 | 113.23 (13) | C1—S1—C8 | 95.70 (8) |
D—H···A | D—H | H···A | D···A | D—H···A |
C10—H10···N2i | 0.98 | 2.64 | 3.405 (2) | 136 |
C2—H2···O1ii | 0.93 | 2.64 | 3.538 (2) | 161 |
C5—H5···O2 | 0.93 | 2.43 | 3.135 (2) | 132 |
Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) x−1/2, y, −z+3/2. |
Acknowledgements
The authors thank the Unit of Support for Technical and Scientific Research (UATRS, CNRST) for the X-ray measurements and the University Mohammed V, Rabat, Morocco, for financial support.
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