Spontaneous resolution and crystal structure of (2S)-2-(3-nitrophenyl)-3-phenyl-2,3,5,6-tetrahydro-4H-1,3-thiazin-4-one; crystal structure of rac-2-(4-nitrophenyl)-3-phenyl-2,3,5,6-tetrahydro-4H-1,3-thiazin-4-one

One of the racemic title isomers crystallized in a centrosymmetric space group and the other spontaneously resolved into enantiomers.

The crystal structures of isomeric rac-2-(4-nitrophenyl)-3-phenyl-2,3,5,6-tetrahydro-4H-1,3-thiazin-4-one (C 16 H 14 N 2 O 3 S) (1) and (2S)-2-(3-nitrophenyl)-3phenyl-2,3,5,6-tetrahydro-4H-1,3-thiazin-4-one (C 16 H 14 N 2 O 3 S) (2) are reported here. While 1 crystallizes in a centrosymmetric space group, the crystal of 2 chosen for data collection has molecules only with (2S) chirality. This is the result of spontaneous resolution during crystallization, as the synthesis produces a racemic mixture. A crystal with (2R) molecules was also found in the same crystallization vial (structure factors available). The six-membered thiazine ring in both 1 and 2 displays an envelope conformation with the S atom forming the flap. The aryl rings in both structures adopt an approximate V shape with angles between their planes of 46.97 (14) in 1 and 58.37 (10) in 2. In both structures, the molecules form layers in the ab plane. Within such a layer in 1, one of the O atoms of the nitrophenyl group accepts a C-HÁ Á ÁO hydrogen bond from the CH group at position 5 of the thiazine ring of a molecule of opposite chirality, forming chains along the a-axis direction. Each of the thiazine rings also participate in C-HÁ Á ÁO bonds with the same carbon atom as above, resulting in chains along the b-axis direction, albeit of monochiral type. Adjacent layers are consolidated along the c-axis direction by pairs of parallel hydrogen bonds (C-HÁ Á ÁO type) between the nitrophenyl groups of enantiomers. In 2, the two C-HÁ Á ÁO hydrogen bonds contribute to chain formation along the b-axis direction. Weak edge-to-face interactions between the aryl groups of neighbouring molecules in 1, and C-HÁ Á Á interactions between a thiazine ring CH group and a phenyl group of a neighboring molecule in 2 are also observed.
The spontaneous resolution of a racemic solution by direct crystallization to form a conglomerate, a mechanical mixture of separate homochiral crystals, is an uncommon but wellknown phenomenon, recognized first by Pasteur in 1848 (Pasteur, 1848;Jacques et al., 1981;Eliel & Wilen, 1994;Pé rez-Garcia & Amabilino, 2007). It has even been used in the production of chiral active pharmaceutical ingredients (Bredikhin & Bredikhina, 2017). However, the reasons why this occurs with a minority of molecules are not well understood (Pé rez-Garcia & Amabilino, 2007) and have not yet yielded to attempts to predict occurrence (D'Oria, Karanertzanis & Price, 2010;Pé rez-Garcia & Amabilino, 2007).

Supramolecular features
In both structures, C-HÁ Á ÁO interactions are observed (Tables 1 and 2, Figs. 3 and 4), resulting in layering of molecules in planes parallel to (001). In each layer of structure 1, one of the oxygen atoms of the nitrophenyl group accepts a C-HÁ Á ÁO hydrogen bond from the CH group at position 5 of the thiazine ring of a molecule of opposite chirality. This results in infinite chains of mixed chirality along the a-axis direction. The second oxygen atom of the nitrophenyl group also accepts a hydrogen bond from the thiazine 5-carbon atom, resulting this time in monochiral chains along the b-axis direction. Further, the stacking of layers along the c-axis direction is consolidated by pairs of parallel hydrogen bonds between the nitrophenyl groups of enantiomers. In 2, a monochiral structure, the C-HÁ Á ÁO hydrogen bonds between the chiral carbon atom and the 4-oxygen atom on the neigh-  The molecular structure of 2, with displacement ellipsoids drawn at the 50% probability level.

Figure 1
The molecular structure of 1, with displacement ellipsoids drawn at the 50% probability level. boring thiazine ring results in a chain along the b-axis direction. The second hydrogen bond loops back to the second molecule in the reverse direction of the same chain. While weak edge-to-face interactions [CgÁ Á ÁCg distance of 5.340 (3) Å and an interplanar angle of 84.99 (2) ] between the aryl groups of neighboring molecules is observed in 1, in 2, the 6-carbon atom of the thiazine ring interacts with the phenyl group in a C-HÁ Á Á type interaction [C4Á Á ÁCg = 3.581 (2) Å ].

Synthesis and crystallization
General: A two-necked 25 ml round-bottom flask was ovendried, cooled under N 2 , and charged with a stir bar and the imine (6 mmol). 3-Mercaptopropionic acid (0.52 ml, 6 mmol) and then 2-methyltetrahydrofuran (2.3 ml) were added and the solution was stirred. Pyridine (1.95 ml, 24 mmol) and finally, 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane-2,4,6trioxide (T3P) in 2-methyltetrahydrofuran (50 weight percent; 7.3 ml, 12 mmol) were added. The reaction was stirred at room temperature and followed by TLC. The mixture was poured into a separatory funnel with dichloromethane and distilled water. The layers were separated and the aqueous was then extracted twice with dichloromethane. The organics were combined and washed with saturated sodium bicarbonate and then saturated sodium chloride. The organic was dried over sodium sulfate and concentrated under vacuum to give crude product.

Figure 3
Packing diagram for 1, showing the layering of molecules in the ab plane. Red dotted lines show hydrogen bonds between enantiomers and blue dotted lines show interactions between molecules of same chirality.

Figure 4
Packing diagram for 2, showing the layering of molecules in the ab plane. Blue dotted lines show hydrogen bonds between molecules forming a chain in the b-axis direction and red dotted lines show a loop-back interaction within each chain.

Refinement
Crystal data, data collection and structure refinement details for both structures 1 and 2 are summarized in Table 3. The H atoms were placed geometrically and allowed to ride on their parent C atoms during refinement, with C-H distances of 0.93 Å (aromatic), 0.97 Å (methylene) and 0.98 (methyl) and with U iso (H) = 1.2U eq (aromatic or methylene C) or 1.5U eq (methyl C). In structure 2, the absolute configuration for the chiral centres in the molecule was determined as (2S) with a Flack absolute structure parameter of 0.09 (7) for 4055 Friedel pairs.  (7) Computer programs: SMART and SAINT (Bruker, 2016), olex2.solve (Bourhis et al., 2015), SHELXS97 and SHELXL97 (Sheldrick, 2008) and OLEX2

Special details
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 (10 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 F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2sigma(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

rac-2-(4-Nitrophenyl)-3-phenyl-3,4,5,6-tetrahydro-2H-1,3-thiazin-4-one (2)
Crystal data where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.001 Δρ max = 0.32 e Å −3 Δρ min = −0.16 e Å −3 Absolute structure: Flack (1983), 4055 Friedel pairs Absolute structure parameter: 0.09 (7) Special details 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 (10 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 F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2sigma(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.