rac-2,3-Diphenyl-2,3-di­hydro-4H-pyrido[3,2-e][1,3]thia­zin-4-one 1-oxide

Yennawar, H.P.; Noble, D.J.; Yang, Z.; Silverberg, L.J.

doi:10.1107/S2414314617011129

organic compounds

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ISSN: 2414-3146

Volume 2| Part 8| August 2017| x171112

https://doi.org/10.1107/S2414314617011129

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rac-2,3-Diphenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-one 1-oxide

Hemant P. Yennawar,^a Duncan J. Noble,^b Ziwei Yang ^b and Lee J. Silverberg ^b ^*

^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

Edited by H. Stoeckli-Evans, University of Neuchâtel, Switzerland (Received 21 June 2017; accepted 27 July 2017; online 1 August 2017)

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⋯O_carbonyl 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 crystal structure we have previously reported (Yennawar et al., 2014 ). Herein, we report on the crystal structure 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 .)

Figure 1
The title compound (I) and related compounds.

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 space group 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 ).

Figure 2
The molecular structure of the title compound, with displacement ellipsoids drawn at the 50% probability level..

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.

Table 1
Hydrogen-bond geometry (Å, °)

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) $[-x+{\script{1\over 2}}, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

Figure 3
Crystal packing diagram showing C—H⋯O contacts as dotted red lines between molecules of (I), which form helical chains along b-axis direction.

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 diffraction analysis, were grown by slow evaporation of a solution in toluene.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₉H₁₄N₂O₂S
M_r	334.38
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	298
a, b, c (Å)	9.1633 (15), 11.0861 (18), 16.250 (3)
β (°)	104.011 (3)
V (Å³)	1601.7 (5)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.22
Crystal size (mm)	0.29 × 0.15 × 0.05

Data collection
Diffractometer	Bruker CCD area detector
Absorption correction	Multi-scan (SADABS; Bruker, 2001 )
T_min, T_max	0.794, 0.9
No. of measured, independent and observed [I > 2σ(I)] reflections	10735, 3917, 3163
R_int	0.024
(sin θ/λ)_max (Å⁻¹)	0.667

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.049, 0.150, 1.07
No. of reflections	3917
No. of parameters	217
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.38, −0.34
Computer programs: SMART and SAINT (Bruker, 2001), SHELXS and SHELXL (Sheldrick, 2008 ) and OLEX2 (Dolomanov et al., 2009 ).

Structural data

CCDC reference: 1565252

Crystal structure: contains datablocks I, Global. DOI: https://doi.org/10.1107/S2414314617011129/su5380sup1.cif

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

checkCIF report

Computing details top

Data collection: SMART (Bruker, 2001); cell refinement: 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).

2,3-Diphenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-one 1-oxide top

Crystal data top

C₁₉H₁₄N₂O₂S	F(000) = 696
M_r = 334.38	D_x = 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

Data collection top

Bruker CCD area detector diffractometer	3917 independent reflections
Radiation source: fine-focus sealed tube	3163 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.024
phi and ω scans	θ_max = 28.3°, θ_min = 2.3°
Absorption correction: multi-scan (SADABS; Bruker, 2001)	h = −7→12
T_min = 0.794, T_max = 0.9	k = −14→14
10735 measured reflections	l = −21→20

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)] = 0.049	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.150	H-atom parameters constrained
S = 1.07	w = 1/[σ²(F_o²) + (0.1P)²] where P = (F_o² + 2F_c²)/3
3917 reflections	(Δ/σ)_max < 0.001
217 parameters	Δρ_max = 0.38 e Å⁻³
0 restraints	Δρ_min = −0.34 e Å⁻³

Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
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)

Atomic displacement parameters (Å²) top

	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)

Geometric parameters (Å, º) top

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)

Hydrogen-bond geometry (Å, º) top

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.

References

Arya, K., Tomar, P. & Singh, J. (2014). RSC Adv. 4, 3060–3064. Web of Science CrossRef CAS Google Scholar
Bruker (2001). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Cannon, K., Gandla, D., Lauro, S., Silverberg, L., Tierney, J. & Lagalante, A. (2015). Intl. J. Chem. (Toronto, ON, Can.), 7(2), 73–84. Google Scholar
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
Gududuru, V., Hurh, E., Dalton, J. T. & Miller, D. D. (2004). Bioorg. Med. Chem. Lett. 14, 5289–5293. Web of Science CrossRef PubMed CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Silverberg, L. J., Pacheco, C. N., Lagalante, A., Cannon, K. C., Bachert, J. T., Xie, Y., Baker, L. & Bayliff, J. A. (2015). Intl. J. Chem. (Toronto, ON, Can.), 7(2), 150-162. Google Scholar
Surrey, A. R. (1963). US Patent 3082209. Google Scholar
Surrey, A. R., Webb, W. G. & Gesler, R. M. (1958). J. Am. Chem. Soc. 80, 3469–3471. CrossRef CAS Web of Science Google Scholar
Yennawar, H. P., Fox, R., Moyer, Q. J., Yang, Z. & Silverberg, L. J. (2017). Acta Cryst. E73 1189–1191. CSD CrossRef IUCr Journals Google Scholar
Yennawar, H. P., Singh, H. & Silverberg, L. J. (2014). Acta Cryst. E70, o638. CSD CrossRef IUCr Journals Google Scholar
Yennawar, H. P., Yang, Z. & Silverberg, L. J. (2016). Acta Cryst. E72, 1541–1543. Web of Science CSD CrossRef IUCr Journals Google Scholar

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