Synthesis and crystal structures of two racemic 2-heteroaryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones

3-Phenyl-2-(thiophen-3-yl)-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-one (C17H12N2OS2, 1) and 2-(1H-indol-3-yl)-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-one 0.438-hydrate (C21H15N3OS·0.438H2O, 2) crystallize in space groups P21/n and C2/c, respectively. The asymmetric unit in each case is comprised of two parent molecules, albeit of mixed chirality in the case of 1 and of similar chirality in 2 with the enantiomers occupying the neighboring asymmetric units. Structure 2 also has water molecules (partial occupancies) that form continous channels along the b-axis direction.


Structural commentary
The title compounds crystallize in monoclinic lattices with two independent molecules (A containing C1 in 1 and 2, and B containing C18 in 1 and C22 in 2; Figs. 1 and 2) in their respective asymmetric units.In 1, molecules of both chiralities are seen, while in 2 both molecules of similar chirality occupy the asymmetric unit.In each structure the independent molecules (with appropriate inversion applied in 1) have almost identical configuration, as was confirmed by the alignment RMSD values falling within 0.013 A ˚when superposing chirally similar molecules and matching the three non-H atoms surrounding the 2-carbon.In 2, four disordered water molecule sites were identified in difference-Fourier maps and refined well with manually adjusted quarter occupancy each.However, one of those oxygen atoms sits on a special position (multiplicity 2) resulting in a total contribution of 0.875 water molecules per asymmetric unit (or about 0.438 water molecules per parent molecule).The core thiazine ring in both structures exhibits an envelope conformation with the 2carbon forming the flap [puckering amplitude Q ranging between 0.5545 (15) and 0.631 (2) A ˚, and the � and ' values, after accounting for the absolute configuration transformations, are between 61.47 (17) and 66.50 (18) � , and 35.6 (2) and 47.14 (2) � , respectively].

Supramolecular features
In 1, the intermolecular interactions are defined solely by hydrogen bonds (Table 1,

Figure 1
The molecular structure of 1 with displacement ellipsoids drawn at the 50% probability level.Molecules of both chirality are seen.The thiophene ring of molecule B exhibits a rotational disorder.

Figure 2
The molecular structure of 2 with displacement ellipsoids drawn at the 50% probability level.Both molecules have the same chirality.The water O atoms (O3 to O6) at quarter occupancy each were refined without protons.

Table 1
Hydrogen-bond geometry (A ˚, � ) for 1.In 2, there are two types of hydrogen-bond interactions as well (Table 2,

Synthesis and crystallization
General: TLC plates (silica gel GF, 250-micron, 10 x 20 cm, cat.No. P21521) were purchased from Miles Scientific.TLCs were visualized under short wave UV, and then with I 2 , and then by spraying with ceric ammonium nitrate/sulfuric acid and heating.Infrared spectra were run on a Thermo-Fisher NICOLET iS50 FT-IR using a diamond-ATR attachment for direct powder analysis (Penn State Schuylkill). 1 H and 13 C NMR experiments (Penn State's shared NMR facility, University Park) were carried out on a Bruker Avance-III-HD 500.20-MHz( 1 H frequency) instrument using a 5 mm Prodigy (liquid nitrogen cooled) BBOBB-1 H/ 19 F/D Z-GRD cryoprobe.Samples were dissolved in pyridine-d5 and analyzed at RT.Typical conditions for 1 H acquisition were 1 s relaxation delay, acquisition time of 3.28 s, and spectral width of 10 kHz, 32 scans.Spectra were zero-filled to 128k points, and multiplied by exponential multiplication (EM with LB = 0.3 Hz) prior to FT.For 13 C experiments, data were acquired with power-gated 1 H decoupling using a 2 s relaxation delay, with an acquisition time of 1.1 s, spectral width of 29.8 kHz, and 256 scans.Spectra were zero-filled once, and multiplied by EM with LB = 2 Hz prior to FT. MS samples were analyzed for purity and accurate mass by LCMS on a SCIEX Exion LC with a SCIEX 5600+ TripleTOF MS.Separation was achieved on an Agilent Infinity LabPoroshell column 120 EC-C18, 2.1 X 50mm, 2.7-micron particle (p/n 699775-902), column maintained at 313 K. Elution using a reversed phase gradient of 100% (water with 0.1% formic acid)ramped to 100% (acetonitrile with 0.1% formic acid) over 10 min at a flowrate of 0.4m L min À 1 .The MS was scanned over 50-1200 Da and calibrated with the SCIEX APCI positive calibrant solution (Part 4460131) prior to sample analysis.Samples were analyzed in ESI positive mode with a DP = 100 V, CE = 10, GAS1 = GAS2 = 60 psi, curtain = 30 psi, ISV = 5500 V, and source temperature of 773 K (Villanova University).Melting points were performed on a Vernier Melt Station (Penn State Schuylkill).Suitable crystals were selected and sequentially mounted using a nylon loop and a dab of paratone oil on a Rigaku Oxford diffraction, Synergy Custom system, HyPix-Arc 150 diffractometer at Penn State, University Park.The  crystals were frozen to 173 (2) K during data collection.Using OLEX2, the structures were solved with the SHELXT (Sheldrick, 2015a) structure solution program using Intrinsic Phasing and refined with the SHELXL (Sheldrick, 2015b) refinement package using least-squares minimization.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3.
For refining structure 1 that has the rotational-flip of the thiophene ring, rigid-group disorder, geometric and atomicdisplacement restraints (RIGU, DFIX, SADI, SIMU, DELU and ISOR) were used to achieve the convergence.
The refinement of structure 2 involved four partially occupied water molecules identified from the difference-Fourier map and their occupancies manually adjusted to 0.25 each.Placing the hydrogen atoms on the water molecules resulted in high shift/esd values and so were excluded.ISOR restraint for all the four water oxygens and for C10, C11 atoms of phenyl ring in molecule A and C38 and C39 atoms in the indole ring of molecule B, as well as SIMU and DELU for all atoms in the structure, helped converge the refinement.In both above structures, hydrogen atoms were placed at calculated positions and refined using a riding model.

Special details
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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å
Fig. 3) of two types -the C-H� � �O type where a carbon atom of the thiophene ring in molecule A donates a proton to the only oxygen of its translational neighbour [C4-H4� � �O1 = 3.168 (2) A ˚, 164.5 � ] and the C-H� � �N type where the 2-carbon of the thiazine in molecule B donates a proton to the lone pair on the nitrogen of fused pyridine ring of its independent neighbor i.e. molecule A [C18-H18� � �N2 = 3.494 (2) A ˚, 167.1 � ].The C-H� � �N type interactions are considered weak, but Webber et al. (2020) have studied their strengths.No �-� stacking interactions between rings of the neighboring molecules were observed in this structure.
Fig. 4).One is an N-H� � �O type hydrogen bond [N3-H3� � �O2 = 2.828 (3) A ˚, 160.7 � ] where the nitrogen of the indole ring of molecule A donates a proton to the oxygen of enantiomeric molecule B. The other is a reciprocal pair of C-H� � �N(�) hydrogen bonds where a carbon from the fused pyridine ring donates a proton to the � electron cloud over the nitrogen atom in the indole ring, connecting two enantiomers of molecule B in a give-and-take fashion [C26-H26� � �N6 = 3.463 (3) A ˚, 155.1 � ].In the extended structure, the hydrogen bonds of both types result in the assembly of continuous molecular chains in the [101] direction.Unlike the crystal of 1, this one is further stabilized by �-� stacking interactions between pyridine rings of symmetry-related molecules [the centroid-centroid distance and slippage are 3.5677 (16) and 1.017A ˚, respectively].These ring overlaps resemble the teeth of a zipper, binding the adjacent parallel molecular chains.Continuous water channels along the b-axis direction punctuate the 'teeth', in an alternating fashion.

Figure 3
Figure 3 Packing diagram for 1 showing C-H� � �O and C-H� � �N type hydrogen bonds between molecules.

Figure 4
Figure 4 Packing diagram for 2 viewing down the b-axis, showing N-H� � �O and C-H� � �N hydrogen bonds between molecules.The �-� stacking interactions that hold adjacent parallel chains akin to the teeth of a zipper and partially occupied water molecules forming continuous channels down the b-axis are also seen.

Table 3
Experimental details.