Crystal structure of rac-2,3-diphenyl-2,3,5,6-tetrahydro-4H-1,3-thiazin-4-one 1-oxide.

In the title compound, C16H15NO2S [alternative name: rac-2,3-diphenyl-1,3-thia-zinan-4-one 1-oxide], the thia-zine ring exhibits an envelope conformation, with the S atom forming the flap. The sulfoxide O atom is in a pseudo-axial position on the thia-zine ring and is trans to the phenyl group on C-2. The phenyl rings form a dihedral angle of 89.47 (19)°. In this racemate crystal, homochiral mol-ecules form slabs parallel to (010) of thickness b/2 which then stack with alternating chirality in the b-axis direction. The stacking is aided by edge-to-face inter-actions between the phenyl rings of racemic mol-ecules. Within each of the single-enanti-omer slabs, the mol-ecules are held by C-H⋯O-type inter-actions, with an H⋯O distance of 2.30 Å, forming infinite chains along the c-axis direction, as well by the edge-to-face inter-actions between phenyl rings of neighboring mol-ecules in the a-axis direction.

Chemical context

1,3-Thia­zin-4-ones are a group of six-membered heterocycles with a wide range of biological activity (Ryabukhin et al., 1996 ▸). Surrey’s research (Surrey et al., 1958 ▸; Surrey, 1963a ▸) resulted in the discovery of two drugs, the anti-anxiety and muscle relaxant chlormezanone [2-(4-chloro­phen­yl)-3-methyl-2,3,5,6-tetra­hydro-4H-1,3-thia­zin-4-one 1,1-dioxide; Merck Index, 2006 ▸; Tanaka & Hirayama, 2005 ▸] and muscle relaxant dichlormezanone [2-(3,4-di­chloro­phen­yl)-3-methyl-2,3,5,6-tetra­hydro-4H-1,3-thia­zin-4-one 1,1-dioxide; Dictionary of Drugs, 1990 ▸]. These sulfones showed greater activity than the sulfides from which they were synthesized (Surrey et al., 1958 ▸). Surrey also prepared a variety of other sulfoxides and sulfones of 3-alkyl-2-aryl-2,3,5,6-tetra­hydro-4H-1,3-thia­zin-4-ones (Surrey, 1963a ▸,b ▸). Surrey did not successfully synthesize any 2-aryl-3-aryl-2,3,5,6-tetra­hydro-4H-1,3-thia­zin-4-ones (Silverberg et al., 2015 ▸), and to the best of our knowledge nobody has reported any oxides of this type of compound. We previously reported the crystal structure of 2,3-diphenyl-2,3,5,6-tetra­hydro-4H-1,3-thia­zin-4-one (Yennawar & Silverberg, 2014 ▸). Herein, we report the crystal structure of that compound’s sulfoxide, prepared using the method we have previously reported for oxidation of the five-membered 1,3-thia­zolidin-4-ones (Cannon et al., 2015 ▸).

Structural commentary

The crystal structure of this racemic compound shows a thia­zine ring in an envelope pucker with puckering amplitude of 0.718 (3) Å (Fig. 1 ▸). The oxygen on sulfur is pseudo-axial on the thia­zine ring. The two phenyl rings, on two adjacent atoms of the thia­zine ring, are perpendicular to each other with an angle of 89.47 (19)° between their planes. The oxygen on sulfur and the phenyl ring on C2 are trans to each other.

Figure 1

The mol­ecular conformation and atom-numbering scheme for the title compound, with non-H atoms shown as 50% probability displacement ellipsoids.

Supra­molecular features

The crystal consists of a racemic mixture of the title compound. The two phenyl groups and one of the two oxygen atoms participate in inter­molecular inter­actions (Table 1 ▸). The mol­ecules of single chirality form slabs in the ac plane aided by π–π edge-to-face inter­actions, with inter-centroid distance of 5.195 (3) Å, in the a-axis direction and with C—H⋯O hydrogen-bonds (Table 1 ▸) in the c-axis direction (Fig. 2 ▸). Along the b-axis direction, these slabs stack with alternating chirality, stabilized once again by π–π edge-to-face inter­actions with inter-centroid distances of 5.021 (3) Å.

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C1—H1⋯O1i	0.98	2.30	3.261 (5)	167

Symmetry code: (i) .

Figure 2

Packing viewed down the c axis. Alternating slabs of enanti­omers along the b-axis direction are differentiated by the color scheme.

Database survey

Crystal structures of a number of 1,3-thia­zolidin-4-one 1-oxides have been reported (Wang et al., 2010 ▸; Johnson et al., 1983 ▸; Chen et al., 2011 ▸; Colombo et al., 2008 ▸; Yennawar et al., 2015 ▸); in each case the oxygen on sulfur and the group on C-2 had a trans relationship, as does the structure reported here. The structure of chlormezanone [2-(4-chloro­phen­yl)-3-methyl-2,3,5,6-tetra­hydro-4H-1,3-thia­zin-4-one 1,1-dioxide] has also been disclosed (Tanaka & Horayama, 2005 ▸). To the best of our knowledge, there have been no published crystal structures of a 2,3,5,6-tetra­hydro-4H-1,3-thia­zin-4-one 1-oxide.

Synthesis and crystallization

A 5 mL round-bottom flask was charged with 50.5 mg of 2,3-diphenyl-2,3,5,6-tetra­hydro-4H-1,3-thia­zin-4-one and 1.5 mL of methanol and stirred. A solution of 85.6 mg Oxone® and 0.74 mL 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 7.4 mL distilled water. The solution was extracted with 7.4 mL di­chloro­methane. The organic layer was washed with distilled water and then with sat. sodium chloride. The solution was dried over Na2SO4 and concentrated under vacuum to a crude solid. This was chromatographed on flash silica gel, eluting with 70% ethyl acetate/hexa­nes, 100% ethyl acetate, and 100% acetone, giving 37.5 mg product (70% yield), m.p.: 396–400 K, R = 0.23 (EtOAc). Crystals for X-ray crystallography were grown by slow evaporation from ethanol solution.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. The hydrogen atoms were placed geometrically and allowed to ride on the carbon atoms during refinement, with C—H distances of 0.98 Å (methine), 0.96 Å (meth­yl) and 0.93 Å (aromatic) and with U iso(H) = 1.2U eq(aromatic and methine C) or 1.5U eq(meth­yl).

Table 2

Experimental details

Crystal data
Chemical formula	C16H15NO2S
M r	285.35
Crystal system, space group	Orthorhombic, P n a21
Temperature (K)	298
a, b, c (Å)	10.547 (4), 17.317 (6), 7.592 (3)
V (Å3)	1386.5 (8)
Z	4
Radiation type	Mo Kα
μ (mm−1)	0.23
Crystal size (mm)	0.23 × 0.18 × 0.16
Data collection
Diffractometer	Bruker SMART APEX CCD area detector
Absorption correction	Multi-scan (SADABS; Bruker, 2001 ▸)
T min, T max	0.636, 0.964
No. of measured, independent and observed [I > 2σ(I)] reflections	11124, 3428, 3182
R int	0.032
(sin θ/λ)max (Å−1)	0.668
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.075, 0.161, 1.26
No. of reflections	3428
No. of parameters	181
No. of restraints	1
H-atom treatment	H-atom parameters constrained
Δρmax, Δρmin (e Å−3)	0.38, −0.27
Absolute structure	Flack (1983 ▸), 4716 Friedel pairs
Absolute structure parameter	0.12 (14)

Computer programs: SMART and SAINT (Bruker, 2001 ▸), SHELXS97 (Sheldrick, 2008 ▸), SHELXL2014 (Sheldrick, 2015 ▸) and OLEX2 (Dolomanov et al., 2009 ▸).

Crystal structure: contains datablock(s) I. DOI: 10.1107/S2056989016015395/gk2665sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989016015395/gk2665Isup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989016015395/gk2665Isup3.mol

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989016015395/gk2665Isup4.cml

CCDC reference: 1507647

Additional supporting information: crystallographic information; 3D view; checkCIF report

C16H15NO2S	Dx = 1.367 Mg m−3
Mr = 285.35	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pna21	Cell parameters from 3661 reflections
a = 10.547 (4) Å	θ = 2.3–26.4°
b = 17.317 (6) Å	µ = 0.23 mm−1
c = 7.592 (3) Å	T = 298 K
V = 1386.5 (8) Å3	Block, colorless
Z = 4	0.23 × 0.18 × 0.16 mm
F(000) = 600

Bruker SMART APEX CCD area detector diffractometer	3428 independent reflections
Radiation source: fine-focus sealed tube	3182 reflections with I > 2σ(I)
Parallel,graphite monochromator	Rint = 0.032
φ and ω scans	θmax = 28.3°, θmin = 2.3°
Absorption correction: multi-scan (SADABS; Bruker, 2001)	h = −13→13
Tmin = 0.636, Tmax = 0.964	k = −20→23
11124 measured reflections	l = −10→10

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.075	H-atom parameters constrained
wR(F2) = 0.161	w = 1/[σ2(Fo2) + (0.0582P)2 + 0.8049P] where P = (Fo2 + 2Fc2)/3
S = 1.26	(Δ/σ)max < 0.001
3428 reflections	Δρmax = 0.38 e Å−3
181 parameters	Δρmin = −0.27 e Å−3
1 restraint	Absolute structure: Flack (1983), 4716 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.12 (14)

Experimental. 1. SADABS was used for absorption correction. R(int) was 0.0424 before and 0.0268 after correction. The Ratio of minimum to maximum transmission is 0.6364. The λ/2 correction factor is 0.0015.2. 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
S1	0.17133 (10)	0.45935 (5)	−1.97816 (14)	0.0469 (3)
O1	0.0575 (3)	0.44303 (18)	−1.8700 (4)	0.0659 (9)
O2	0.0431 (3)	0.23452 (16)	−2.0769 (4)	0.0542 (8)
N1	0.0796 (2)	0.34956 (15)	−2.2011 (4)	0.0281 (6)
C1	0.1326 (3)	0.42779 (19)	−2.2029 (4)	0.0304 (7)
H1	0.0646	0.4619	−2.2442	0.036*
C2	0.1038 (4)	0.2938 (2)	−2.0808 (5)	0.0375 (8)
C3	0.2109 (4)	0.3050 (2)	−1.9494 (5)	0.0483 (10)
H3A	0.1771	0.2936	−1.8334	0.058*
H3B	0.2745	0.2660	−1.9744	0.058*
C4	0.2783 (4)	0.3813 (3)	−1.9375 (5)	0.0521 (11)
H4A	0.3465	0.3828	−2.0231	0.063*
H4B	0.3151	0.3870	−1.8211	0.063*
C5	0.2437 (3)	0.44151 (17)	−2.3232 (4)	0.0278 (6)
C6	0.2671 (4)	0.5164 (2)	−2.3791 (5)	0.0392 (8)
H6	0.2126	0.5559	−2.3446	0.047*
C7	0.3688 (4)	0.5333 (3)	−2.4840 (8)	0.0534 (10)
H7	0.3842	0.5839	−2.5186	0.064*
C8	0.4485 (4)	0.4748 (3)	−2.5384 (6)	0.0517 (11)
H8	0.5175	0.4860	−2.6103	0.062*
C9	0.4261 (3)	0.4006 (2)	−2.4869 (6)	0.0472 (9)
H9	0.4799	0.3613	−2.5247	0.057*
C10	0.3245 (3)	0.3830 (2)	−2.3791 (5)	0.0391 (8)
H10	0.3102	0.3323	−2.3441	0.047*
C11	−0.0254 (3)	0.33887 (18)	−2.3192 (4)	0.0297 (7)
C12	−0.1478 (4)	0.3459 (2)	−2.2599 (5)	0.0408 (8)
H12	−0.1627	0.3562	−2.1415	0.049*
C13	−0.2485 (4)	0.3378 (2)	−2.3733 (6)	0.0477 (10)
H13	−0.3313	0.3424	−2.3323	0.057*
C14	−0.2254 (4)	0.3231 (2)	−2.5468 (5)	0.0439 (9)
H14	−0.2934	0.3171	−2.6236	0.053*
C15	−0.1043 (4)	0.3169 (3)	−2.6103 (5)	0.0492 (10)
H15	−0.0901	0.3077	−2.7294	0.059*
C16	−0.0032 (4)	0.3244 (2)	−2.4953 (5)	0.0454 (9)
H16	0.0794	0.3197	−2.5366	0.055*

	U11	U22	U33	U12	U13	U23
S1	0.0600 (6)	0.0427 (5)	0.0380 (4)	−0.0080 (4)	0.0072 (5)	−0.0128 (4)
O1	0.083 (2)	0.0605 (18)	0.0548 (19)	0.0131 (17)	0.0259 (18)	−0.0026 (16)
O2	0.0614 (18)	0.0366 (15)	0.0648 (19)	−0.0055 (13)	0.0023 (15)	0.0188 (13)
N1	0.0242 (13)	0.0277 (13)	0.0325 (13)	−0.0015 (10)	0.0013 (12)	0.0054 (11)
C1	0.0326 (16)	0.0262 (15)	0.0323 (16)	0.0012 (13)	−0.0013 (14)	0.0026 (13)
C2	0.041 (2)	0.0306 (17)	0.0410 (19)	0.0064 (14)	0.0042 (16)	0.0056 (15)
C3	0.049 (2)	0.055 (2)	0.041 (2)	0.0142 (18)	−0.0079 (18)	0.0038 (18)
C4	0.042 (2)	0.080 (3)	0.034 (2)	−0.003 (2)	−0.0060 (16)	0.0044 (18)
C5	0.0233 (14)	0.0287 (14)	0.0316 (16)	−0.0045 (12)	−0.0070 (12)	0.0007 (13)
C6	0.0376 (19)	0.0357 (17)	0.0441 (19)	−0.0002 (15)	−0.0024 (16)	0.0036 (16)
C7	0.046 (2)	0.057 (2)	0.057 (2)	−0.0126 (18)	0.003 (3)	0.018 (2)
C8	0.0308 (19)	0.081 (3)	0.043 (2)	−0.017 (2)	0.0064 (16)	0.006 (2)
C9	0.0275 (16)	0.064 (2)	0.051 (2)	−0.0013 (16)	0.0053 (19)	−0.012 (2)
C10	0.0344 (19)	0.0370 (17)	0.046 (2)	−0.0008 (14)	−0.0017 (16)	−0.0019 (17)
C11	0.0333 (17)	0.0266 (14)	0.0293 (15)	0.0000 (12)	−0.0056 (14)	−0.0002 (13)
C12	0.0364 (19)	0.047 (2)	0.0388 (19)	−0.0003 (16)	0.0021 (15)	0.0013 (17)
C13	0.0287 (18)	0.055 (2)	0.059 (2)	−0.0006 (17)	0.0004 (18)	−0.002 (2)
C14	0.042 (2)	0.040 (2)	0.050 (2)	−0.0065 (16)	−0.0185 (17)	0.0007 (17)
C15	0.048 (2)	0.073 (3)	0.0261 (17)	−0.004 (2)	−0.0027 (17)	−0.0071 (18)
C16	0.0369 (18)	0.062 (2)	0.0374 (19)	−0.0022 (16)	0.0089 (17)	−0.0001 (19)

S1—O1	1.482 (3)	C5—C10	1.390 (5)
S1—C1	1.838 (4)	C6—C7	1.368 (6)
S1—C4	1.787 (5)	C7—C8	1.379 (6)
O2—C2	1.210 (5)	C8—C9	1.364 (6)
N1—C1	1.466 (4)	C9—C10	1.383 (5)
N1—C2	1.354 (4)	C11—C12	1.372 (5)
N1—C11	1.436 (4)	C11—C16	1.380 (5)
C1—C5	1.505 (5)	C12—C13	1.375 (6)
C2—C3	1.519 (5)	C13—C14	1.363 (6)
C3—C4	1.503 (6)	C14—C15	1.370 (6)
C5—C6	1.387 (5)	C15—C16	1.384 (6)
O1—S1—C1	106.12 (18)	C6—C5—C10	118.7 (3)
O1—S1—C4	105.8 (2)	C10—C5—C1	123.2 (3)
C4—S1—C1	94.34 (17)	C7—C6—C5	121.1 (4)
C2—N1—C1	126.4 (3)	C6—C7—C8	119.7 (4)
C2—N1—C11	118.4 (3)	C9—C8—C7	120.1 (4)
C11—N1—C1	114.0 (2)	C8—C9—C10	120.7 (4)
N1—C1—S1	110.6 (2)	C9—C10—C5	119.7 (3)
N1—C1—C5	116.7 (3)	C12—C11—N1	120.6 (3)
C5—C1—S1	110.1 (2)	C12—C11—C16	119.5 (3)
O2—C2—N1	121.4 (3)	C16—C11—N1	119.8 (3)
O2—C2—C3	119.0 (3)	C11—C12—C13	120.8 (4)
N1—C2—C3	119.5 (3)	C14—C13—C12	119.1 (4)
C4—C3—C2	120.2 (3)	C13—C14—C15	121.4 (4)
C3—C4—S1	110.9 (3)	C14—C15—C16	119.3 (4)
C6—C5—C1	118.1 (3)	C11—C16—C15	119.9 (3)
S1—C1—C5—C6	−76.3 (3)	C2—N1—C11—C16	−109.6 (4)
S1—C1—C5—C10	102.9 (3)	C2—C3—C4—S1	34.5 (4)
O1—S1—C1—N1	−49.2 (3)	C4—S1—C1—N1	58.6 (3)
O1—S1—C1—C5	−179.5 (2)	C4—S1—C1—C5	−71.7 (3)
O1—S1—C4—C3	46.9 (3)	C5—C6—C7—C8	1.3 (7)
O2—C2—C3—C4	−173.1 (4)	C6—C5—C10—C9	0.6 (5)
N1—C1—C5—C6	156.6 (3)	C6—C7—C8—C9	−0.3 (7)
N1—C1—C5—C10	−24.1 (4)	C7—C8—C9—C10	−0.5 (7)
N1—C2—C3—C4	8.0 (5)	C8—C9—C10—C5	0.3 (6)
N1—C11—C12—C13	178.2 (3)	C10—C5—C6—C7	−1.4 (6)
N1—C11—C16—C15	−177.7 (3)	C11—N1—C1—S1	139.1 (2)
C1—S1—C4—C3	−61.2 (3)	C11—N1—C1—C5	−94.1 (3)
C1—N1—C2—O2	170.2 (3)	C11—N1—C2—O2	3.5 (5)
C1—N1—C2—C3	−11.0 (5)	C11—N1—C2—C3	−177.6 (3)
C1—N1—C11—C12	−95.3 (4)	C11—C12—C13—C14	−0.3 (6)
C1—N1—C11—C16	82.2 (4)	C12—C11—C16—C15	−0.1 (6)
C1—C5—C6—C7	177.9 (4)	C12—C13—C14—C15	−0.6 (6)
C1—C5—C10—C9	−178.7 (3)	C13—C14—C15—C16	1.1 (7)
C2—N1—C1—S1	−28.1 (4)	C14—C15—C16—C11	−0.8 (6)
C2—N1—C1—C5	98.7 (4)	C16—C11—C12—C13	0.7 (6)
C2—N1—C11—C12	72.9 (4)

D—H···A	D—H	H···A	D···A	D—H···A
C1—H1···O1i	0.98	2.30	3.261 (5)	167