organic compounds
rac-2,3-Diphenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-one 1-oxide
aDepartment of Biochemistry and Molecular Biology, Pennsylvania State University, University Park PA 16802, and bPennsylvania State University, Schuylkill Campus, 200 University Drive, Schuylkill Haven, PA 17972, USA
*Correspondence e-mail: ljs43@psu.edu
In the title compound, C19H14N2O2S, the thiazine ring exhibits a screw-boat pucker. The oxygen atom on the sulfur atom of the ring is pseudo-axial on the thiazine ring. In the crystal, 21 screw-related molecules are linked by C—H⋯Ocarbonyl hydrogen bonds, forming helices propagating along the b-axis direction.
Keywords: crystal structure; pyridothiazine; benzothiazine; screw-boat puckering; C–H⋯O hydrogen bonding..
CCDC reference: 1565252
Structure description
Pyridothiazinones (including different positions of the pyridine nitrogen) exhibit a variety of different of biological activities (Arya et al., 2014). The number of 3-aryl-2,3-dihydro-4H-pyrido[3,2-e]thiazin-4-ones reported in the literature is small. One such compound is 2,3-diphenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-one (II) (Fig. 1), whose we have previously reported (Yennawar et al., 2014). Herein, we report on the of that compound's sulfoxide, (I), prepared using the method we have reported for oxidation of five-membered 1,3-thiazolidin-4-ones (Cannon et al., 2015; Silverberg et al., 2015). To the best of our knowledge, this is the first report of an S-oxide of a 2,3-dihydro-4H-pyrido[3,2-e]thiazin-4-one, despite the evidence of enhanced activity in similar 2,3,5,6-tetrahydro-4H-1,3-thiazin-4-ones (Surrey et al., 1958; Surrey, 1963, US Patent 3082209) and in 1,3-thiazolidin-4-ones (Gududuru et al. 2004.)
Although the chemical structure of the title compound, (I) (Fig. 2), differs slightly from the structure of 2,3-diphenyl-2,3-dihydro-4H-1,3-benzothiazin-4-one 1-oxide (III) (Yennawar et al. 2017), both compounds crystallize in the monoclinic P21/n, with very similar unit-cell parameters. Their crystal structures are nearly identical. The thiazine ring in both compounds has a screw-boat conformation [puckering parameters for (I): (Q) = 0.6996 (13) Å, θ = 114.66 (12)° and φ = 205.32 (14)°; puckering parameters for (III): (Q) = 0.686 (2) Å, θ = 114.37 (17)° and φ = 210.6 (2) °]. Atom O1, on the sulfur atom, S1, of the thiazine ring is pseudo-axial on the thiazine ring and trans to the phenyl ring on C1, as observed for (III) and 2,3-diphenyl-2,3,5,6-tetrahydro-4H-1,3-thiazin-4-one 1-oxide (IV) (Yennawar et al., 2016).
The crystal packing of the title compound (I), is identical to that observed for compound (III), hence the supramolecular features are common to both. Molecules related by a 21 screw axis are linked by C1—H1⋯O2i hydrogen bonds, forming helices propagating along the b-axis direction (Table 1 and Fig. 3). While C—H⋯O type interactions are also present in compound (IV), here the oxygen at position 1 (⋯O=S) is the acceptor of the H atom at the chiral C atom, thus forming helices propagating along the c-axis direction. The helices are linked by C—H⋯π interactions forming a three-dimensional supramolecular structure. In compound (II), there are no C—H⋯O hydrogen bonds present, only C—H..π interactions.
Synthesis and crystallization
A 5 ml round-bottom flask was charged with 49.5 mg of 2,3-diphenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-one and 1 ml of methanol and the mixture stirred. A solution of 75.5 mg Oxone® and 0.63 ml of distilled water was added dropwise, and the mixture was stirred until the reaction was complete, as determined by TLC. The solids were dissolved by addition of 6.3 ml distilled water. The solution was extracted twice with dichloromethane. The combined organic phases were washed with a sat. sodium chloride solution. The solution was dried over Na2SO4 and concentrated under vacuum to give a crude solid. Recrystallization from CH2Cl2/hexanes gave 35.5 mg of the title compound (68% yield, m.p. 450–551 K). Colourless thin plate-like crystals, suitable for X-ray were grown by slow evaporation of a solution in toluene.
Refinement
Crystal data, data collection and structure .
details are summarized in Table 2Structural data
CCDC reference: 1565252
https://doi.org/10.1107/S2414314617011129/su5380sup1.cif
contains datablocks I, Global. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314617011129/su5380Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2414314617011129/su5380Isup3.mol
Supporting information file. DOI: https://doi.org/10.1107/S2414314617011129/su5380Isup4.cml
Data collection: SMART (Bruker, 2001); cell
SAINT (Bruker, 2001); data reduction: SAINT (Bruker, 2001); program(s) used to solve structure: SHELXS (Sheldrick, 2008); program(s) used to refine structure: SHELXL (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).C19H14N2O2S | F(000) = 696 |
Mr = 334.38 | Dx = 1.387 Mg m−3 |
Monoclinic, P21/n | Mo Kα radiation, λ = 0.71073 Å |
a = 9.1633 (15) Å | Cell parameters from 3767 reflections |
b = 11.0861 (18) Å | θ = 2.3–28.2° |
c = 16.250 (3) Å | µ = 0.22 mm−1 |
β = 104.011 (3)° | T = 298 K |
V = 1601.7 (5) Å3 | Plate, colorless |
Z = 4 | 0.29 × 0.15 × 0.05 mm |
Bruker CCD area detector diffractometer | 3917 independent reflections |
Radiation source: fine-focus sealed tube | 3163 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.024 |
phi and ω scans | θmax = 28.3°, θmin = 2.3° |
Absorption correction: multi-scan (SADABS; Bruker, 2001) | h = −7→12 |
Tmin = 0.794, Tmax = 0.9 | k = −14→14 |
10735 measured reflections | l = −21→20 |
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)] = 0.049 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.150 | H-atom parameters constrained |
S = 1.07 | w = 1/[σ2(Fo2) + (0.1P)2] where P = (Fo2 + 2Fc2)/3 |
3917 reflections | (Δ/σ)max < 0.001 |
217 parameters | Δρmax = 0.38 e Å−3 |
0 restraints | Δρmin = −0.34 e Å−3 |
Experimental. The data collection nominally covered a full sphere of reciprocal space by a combination of 4 sets of ω scans each set at different φ and/or 2θ angles and each scan (5 s exposure) covering -0.300° degrees in ω. The crystal to detector distance was 5.82 cm. |
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. |
x | y | z | Uiso*/Ueq | ||
C1 | 0.30471 (18) | 0.62077 (13) | 0.18068 (9) | 0.0335 (3) | |
H1 | 0.3135 | 0.5530 | 0.2203 | 0.040* | |
C2 | 0.15996 (18) | 0.81146 (13) | 0.16516 (9) | 0.0324 (3) | |
C3 | 0.17155 (17) | 0.81522 (14) | 0.07510 (9) | 0.0323 (3) | |
C4 | 0.18742 (18) | 0.71236 (14) | 0.02869 (9) | 0.0349 (3) | |
C5 | 0.1838 (2) | 0.81999 (19) | −0.09076 (11) | 0.0518 (5) | |
H5 | 0.1890 | 0.8227 | −0.1472 | 0.062* | |
C6 | 0.1664 (2) | 0.92662 (17) | −0.05124 (11) | 0.0495 (5) | |
H6 | 0.1588 | 0.9992 | −0.0807 | 0.059* | |
C7 | 0.16044 (19) | 0.92452 (15) | 0.03313 (10) | 0.0405 (4) | |
H7 | 0.1491 | 0.9958 | 0.0612 | 0.049* | |
C8 | 0.19571 (18) | 0.70036 (13) | 0.29588 (9) | 0.0337 (3) | |
C9 | 0.0847 (2) | 0.62118 (17) | 0.30533 (11) | 0.0438 (4) | |
H9 | 0.0341 | 0.5745 | 0.2598 | 0.053* | |
C10 | 0.0496 (2) | 0.6120 (2) | 0.38294 (12) | 0.0572 (5) | |
H10 | −0.0258 | 0.5596 | 0.3898 | 0.069* | |
C11 | 0.1271 (3) | 0.6812 (2) | 0.45089 (13) | 0.0600 (6) | |
H11 | 0.1016 | 0.6766 | 0.5028 | 0.072* | |
C12 | 0.2407 (3) | 0.75606 (17) | 0.44173 (11) | 0.0562 (5) | |
H12 | 0.2939 | 0.8003 | 0.4879 | 0.067* | |
C13 | 0.2770 (2) | 0.76636 (15) | 0.36422 (10) | 0.0450 (4) | |
H13 | 0.3547 | 0.8168 | 0.3580 | 0.054* | |
C14 | 0.46180 (18) | 0.65049 (15) | 0.17426 (9) | 0.0359 (4) | |
C15 | 0.5491 (2) | 0.56025 (18) | 0.15151 (12) | 0.0520 (5) | |
H15 | 0.5098 | 0.4829 | 0.1407 | 0.062* | |
C16 | 0.6938 (2) | 0.5836 (2) | 0.14464 (14) | 0.0641 (6) | |
H16 | 0.7504 | 0.5229 | 0.1278 | 0.077* | |
C17 | 0.7537 (2) | 0.6968 (2) | 0.16282 (13) | 0.0647 (6) | |
H17 | 0.8515 | 0.7125 | 0.1589 | 0.078* | |
C18 | 0.6701 (2) | 0.7872 (2) | 0.18682 (12) | 0.0563 (5) | |
H18 | 0.7115 | 0.8635 | 0.1996 | 0.068* | |
C19 | 0.5238 (2) | 0.76419 (17) | 0.19187 (10) | 0.0445 (4) | |
H19 | 0.4668 | 0.8258 | 0.2072 | 0.053* | |
N1 | 0.22476 (15) | 0.71606 (11) | 0.21339 (7) | 0.0322 (3) | |
N2 | 0.19379 (18) | 0.71156 (14) | −0.05230 (9) | 0.0463 (4) | |
O1 | 0.03546 (15) | 0.55035 (11) | 0.09257 (8) | 0.0509 (3) | |
O2 | 0.09481 (14) | 0.89182 (10) | 0.19355 (7) | 0.0454 (3) | |
S1 | 0.18764 (5) | 0.56726 (3) | 0.07754 (2) | 0.03877 (16) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0385 (9) | 0.0304 (7) | 0.0330 (7) | 0.0053 (6) | 0.0113 (6) | 0.0025 (6) |
C2 | 0.0319 (8) | 0.0317 (7) | 0.0320 (7) | 0.0013 (6) | 0.0048 (6) | −0.0022 (5) |
C3 | 0.0278 (8) | 0.0365 (8) | 0.0310 (7) | 0.0015 (6) | 0.0039 (6) | 0.0005 (5) |
C4 | 0.0320 (8) | 0.0404 (8) | 0.0311 (7) | −0.0022 (6) | 0.0049 (6) | −0.0026 (6) |
C5 | 0.0521 (12) | 0.0710 (13) | 0.0306 (8) | −0.0095 (9) | 0.0069 (8) | 0.0035 (8) |
C6 | 0.0508 (11) | 0.0540 (11) | 0.0411 (9) | −0.0012 (8) | 0.0059 (8) | 0.0150 (8) |
C7 | 0.0400 (9) | 0.0399 (9) | 0.0397 (9) | 0.0026 (7) | 0.0060 (7) | 0.0053 (6) |
C8 | 0.0340 (8) | 0.0374 (8) | 0.0298 (7) | 0.0072 (6) | 0.0079 (6) | 0.0017 (6) |
C9 | 0.0359 (9) | 0.0560 (11) | 0.0388 (9) | 0.0003 (8) | 0.0080 (7) | 0.0035 (7) |
C10 | 0.0489 (12) | 0.0719 (13) | 0.0566 (12) | 0.0021 (10) | 0.0240 (9) | 0.0140 (10) |
C11 | 0.0822 (16) | 0.0649 (13) | 0.0404 (10) | 0.0178 (11) | 0.0294 (11) | 0.0062 (8) |
C12 | 0.0882 (16) | 0.0459 (10) | 0.0332 (8) | 0.0089 (10) | 0.0121 (9) | −0.0040 (7) |
C13 | 0.0566 (12) | 0.0395 (9) | 0.0372 (8) | 0.0010 (8) | 0.0082 (8) | −0.0012 (7) |
C14 | 0.0337 (8) | 0.0458 (9) | 0.0282 (7) | 0.0070 (7) | 0.0073 (6) | 0.0077 (6) |
C15 | 0.0470 (11) | 0.0553 (11) | 0.0552 (11) | 0.0148 (8) | 0.0155 (9) | 0.0038 (8) |
C16 | 0.0433 (11) | 0.0910 (17) | 0.0621 (13) | 0.0241 (11) | 0.0205 (10) | 0.0110 (11) |
C17 | 0.0348 (10) | 0.1087 (19) | 0.0510 (11) | 0.0082 (11) | 0.0109 (9) | 0.0279 (11) |
C18 | 0.0426 (11) | 0.0740 (13) | 0.0483 (10) | −0.0096 (10) | 0.0034 (9) | 0.0169 (9) |
C19 | 0.0396 (10) | 0.0509 (10) | 0.0411 (9) | −0.0019 (8) | 0.0060 (7) | 0.0068 (7) |
N1 | 0.0369 (7) | 0.0322 (6) | 0.0280 (6) | 0.0052 (5) | 0.0090 (5) | 0.0007 (5) |
N2 | 0.0489 (9) | 0.0564 (9) | 0.0328 (7) | −0.0077 (7) | 0.0084 (6) | −0.0068 (6) |
O1 | 0.0439 (8) | 0.0531 (7) | 0.0565 (8) | −0.0150 (6) | 0.0139 (6) | −0.0074 (6) |
O2 | 0.0553 (8) | 0.0407 (6) | 0.0408 (6) | 0.0153 (5) | 0.0128 (6) | −0.0013 (5) |
S1 | 0.0433 (3) | 0.0331 (2) | 0.0410 (2) | −0.00253 (16) | 0.01232 (19) | −0.00753 (15) |
C1—C14 | 1.505 (2) | C8—C13 | 1.387 (2) |
C1—N1 | 1.4573 (19) | C8—N1 | 1.4391 (19) |
C1—S1 | 1.8550 (15) | C9—C10 | 1.379 (2) |
C2—C3 | 1.493 (2) | C10—C11 | 1.390 (3) |
C2—N1 | 1.3639 (19) | C11—C12 | 1.367 (3) |
C2—O2 | 1.2232 (18) | C12—C13 | 1.383 (3) |
C3—C4 | 1.394 (2) | C14—C15 | 1.386 (2) |
C3—C7 | 1.382 (2) | C14—C19 | 1.384 (2) |
C4—N2 | 1.331 (2) | C15—C16 | 1.382 (3) |
C4—S1 | 1.7936 (16) | C16—C17 | 1.373 (3) |
C5—C6 | 1.373 (3) | C17—C18 | 1.374 (3) |
C5—N2 | 1.348 (2) | C18—C19 | 1.386 (3) |
C6—C7 | 1.386 (2) | O1—S1 | 1.4847 (13) |
C8—C9 | 1.380 (2) | ||
C14—C1—S1 | 111.16 (10) | C9—C10—C11 | 119.90 (19) |
N1—C1—C14 | 116.13 (13) | C12—C11—C10 | 120.29 (18) |
N1—C1—S1 | 109.24 (10) | C11—C12—C13 | 120.44 (18) |
N1—C2—C3 | 117.41 (13) | C12—C13—C8 | 118.99 (18) |
O2—C2—C3 | 120.42 (14) | C15—C14—C1 | 118.95 (16) |
O2—C2—N1 | 122.16 (14) | C19—C14—C1 | 122.48 (15) |
C4—C3—C2 | 123.29 (14) | C19—C14—C15 | 118.56 (18) |
C7—C3—C2 | 119.59 (14) | C16—C15—C14 | 120.9 (2) |
C7—C3—C4 | 117.07 (14) | C17—C16—C15 | 119.7 (2) |
C3—C4—S1 | 118.89 (12) | C16—C17—C18 | 120.4 (2) |
N2—C4—C3 | 125.13 (15) | C17—C18—C19 | 119.8 (2) |
N2—C4—S1 | 115.85 (12) | C14—C19—C18 | 120.65 (18) |
N2—C5—C6 | 123.61 (16) | C2—N1—C1 | 122.68 (12) |
C5—C6—C7 | 119.04 (16) | C2—N1—C8 | 118.43 (12) |
C3—C7—C6 | 119.15 (15) | C8—N1—C1 | 118.34 (12) |
C9—C8—C13 | 120.92 (16) | C4—N2—C5 | 115.99 (15) |
C9—C8—N1 | 119.23 (14) | C4—S1—C1 | 92.96 (7) |
C13—C8—N1 | 119.84 (15) | O1—S1—C1 | 104.62 (7) |
C10—C9—C8 | 119.36 (17) | O1—S1—C4 | 106.59 (8) |
D—H···A | D—H | H···A | D···A | D—H···A |
C1—H1···O2i | 0.98 | 2.30 | 3.249 (2) | 163 |
Symmetry code: (i) −x+1/2, y−1/2, −z+1/2. |
Acknowledgements
We thank Penn State Schuylkill for financial support and NSF funding (CHEM-0131112) for the X-ray diffractometer.
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