(4RS,6SR)-2-Amino-4-(4-methoxy­phen­yl)-6-phenyl-5,6-dihydro-4H-1,3-thia­zin-3-ium chloride

The title compound, C₁₇H₁₉N₂OS⁺·Cl⁻, was synthesized through a diastereoselective three-component condensation in one pot. The six-membered heterocycle adopts a half-chair conformation which is slightly twisted at 298 K. The cations and the Cl⁻ anions of the structure are connected through a two-dimensional network of N—H...Cl and C—H...Cl hydrogen bonds. Phenyl rings inter­calate between layers, and no π...π stacking is observed in the structure.

Key indicators

• Single-crystal X-ray study
• T = 298 K
• Mean [sigma](C-C) = 0.004 Å
• R factor = 0.056
• wR factor = 0.167
• Data-to-parameter ratio = 17.6

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT220_ALERT_2_C Large Non-Solvent    C     Ueq(max)/Ueq(min) ...       2.69 Ratio
PLAT241_ALERT_2_C Check High      Ueq as Compared to Neighbors for        C16
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for        C12

Alert level G
PLAT793_ALERT_1_G Check the Absolute Configuration of C8     = ...          R
PLAT793_ALERT_1_G Check the Absolute Configuration of C10    = ...          S
PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints .......         18

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   3 ALERT level C = Check and explain
   3 ALERT level G = General alerts; check

   2 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   3 ALERT type 2 Indicator that the structure model may be wrong or deficient
   1 ALERT type 3 Indicator that the structure quality may be low
   0 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

Sulfur-containing heterocyclic compounds represent a type of valuable structure in the heterocycle family. Thiazine is one of the typical heterocyclic structures of this family with multifunctional characters. Among this class of compounds, 1,3-thiazines are of special importance due to their pharmacological activities (Bourzat et al., 1991) and biological characters (Suárez et al., 2006). Presently, there are sevral methodologies developed for synthesizing certain types of 1,3-thiazine derivatives (Barluenga et al., 1991; Sreekumar et al., 1997). We have recently reported a novel three-component approach of building up the 5,6-dihydro-4H-[1,3] thiazine compounds, which starts from aromatic aldehydes, thiourea and styrene with the catalysis of TMSCl (Zhu et al., 2006), as well as a crystal structure of this type (Wan et al., 2006). As a continuous exploration of this novel reaction, we report here the crystal structure of the title compound, a product afforded by the aforementioned diastereoselective three-component condensation (Scheme 1).

The crystal structure analysis shows that the product presents a central heterocycle of 5,6-dihydro-4H-[1,3]thiazin rather than the isomer tetrahydropyrimidine-2(1H)-thione which may give indistinguishable spectral data with the obtained product. From the crystal structure (Figure 1) of the title compound, the core six-member ring 5,6-dihydro-4H-[1,3] thiazin adopts a slightly twisted half-chair conformation.

The general identical bond distances of C11—N1 and C11—N2 [1.314 (3) Å and 1.316 (3) Å, respectively] shows that the bond between C11 and N1 is not a normal C═N double bond, instead, the electron cloud symmetrically distributes between N1, C11 and N2. The total value of bond angles N1—C11—S1, N1—C11—N2 and N2—C11—S1 is 359.94°, which implies that N1, C11, N2, S1 locate in the same plane with a normal deviation of 0.06°. From the 2.4 (3)° torsion angles of S1—N1—C11—C8 and -8.4 (2)° of N1—C11—S1—C10, atoms C8 and C10 (Table 1) are found to be placed in the opposite sides of the plane through N1_S1C11, which also describes the twisted half-chair conformation of this heterocycle. The crystal is mainly stablized by the intermolecular N—H···Cl hydrogen bond, the H atoms at N1 and N2 are involved in the hydrogen bond network and form the crystal packing (Figure 2). Parameters of hydrogen bonds are given in Table 2.

Related literature

For syntheses of related structures, see: Barluenga et al. (1991); Sreekumar et al. (1997). For pharmacological activities and biological characters, see: Bourzat et al. (1991); Suárez et al. (2006). For related novel compounds and structures, see: Wan et al. (2006); Zhu et al. (2006).

S2. Experimental

4-Methoxylbenzaldehyde (5 mmol), styrene (5 mmol) and thiourea (6 mmol) were located in a flask and 5 mmol TMSCl was added, the mixture was then refluxed and stirred in CH₃CN/DMF (3 mL/1.5 mL) for 10 h. The product deposited directly after completion of the reaction and cooling down to room temperature. The solide was filtered and the analytical pure product was afforded by recystalization of the crude product in ethanol. The proper colorless crystal for the X-ray measurement was obtained through slow evaporation of an ethanol solution.

S3. Refinement

H atoms bonded N atoms were located in difference Fourier maps and their parameters were refined with N—H distances restrained to 0.86 (1) Å. The position of the C-bound H atoms were calculated geometrically and refined using a riding model(C—H=0.93–0.98 Å) with U_iso(H) = 1.2U_eq(C).

Computing details

Data collection: SMART (Bruker, 2002); cell refinement: SAINT (Bruker, 2002); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 2002); software used to prepare material for publication: SHELXTL.

Figures

	Fig. 1. Molecular structure of the title compound, showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. Selected N—H^···Cl and C—H^···Cl intermolecular hydrogen bonding interactions along the a-axis, indicated as dashed lines.

(4RS,6SR)-2-Amino-4-(4-methoxyphenyl)-6-phenyl-5,6-dihydro- 4H-[1,3]thiazin-3-ium chloride

Crystal data

C17H19N2OS^+·Cl^−	F(000) = 704
Mr = 334.85	Dx = 1.320 Mg m^−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 3831 reflections
a = 8.4686 (11) Å	θ = 2.2–28.0°
b = 18.341 (2) Å	µ = 0.35 mm^−1
c = 11.1313 (14) Å	T = 298 K
β = 102.971 (2)°	Block, colourless
V = 1684.8 (4) Å^3	0.30 × 0.20 × 0.20 mm
Z = 4

Data collection

CCD area-detector diffractometer	2879 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.083
Graphite monochromator	θmax = 27.0°, θmin = 2.2°
phi and ω scans	h = −10→10
10217 measured reflections	k = −23→11
3673 independent reflections	l = −14→14

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.056	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.167	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	w = 1/[σ^2(Fo^2) + (0.0886P)^2 + 0.2659P] where P = (Fo^2 + 2Fc^2)/3
3673 reflections	(Δ/σ)max < 0.001
209 parameters	Δρmax = 0.56 e Å^−3
18 restraints	Δρmin = −0.31 e Å^−3

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s 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 > σ(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 (Ų)

	x	y	z	Uiso*/Ueq
C1	0.1126 (3)	0.15641 (13)	0.6831 (2)	0.0470 (5)
C2	−0.0516 (3)	0.17089 (14)	0.6538 (3)	0.0592 (6)
H2	−0.0986	0.1945	0.7110	0.071*
C3	−0.1468 (3)	0.15095 (16)	0.5416 (3)	0.0699 (8)
H3	−0.2569	0.1616	0.5235	0.084*
C4	−0.0808 (4)	0.11555 (15)	0.4566 (3)	0.0651 (7)
C5	0.0812 (4)	0.09883 (17)	0.4849 (3)	0.0671 (7)
H5	0.1268	0.0736	0.4286	0.081*
C6	0.1766 (3)	0.11966 (16)	0.5978 (2)	0.0616 (7)
H6	0.2865	0.1085	0.6161	0.074*
C7	−0.1175 (6)	0.0664 (2)	0.2539 (3)	0.1092 (15)
H7A	−0.0385	0.0979	0.2312	0.164*
H7B	−0.2027	0.0568	0.1827	0.164*
H7C	−0.0669	0.0213	0.2853	0.164*
C8	0.2155 (3)	0.18024 (13)	0.8061 (2)	0.0474 (5)
H8	0.1594	0.2203	0.8372	0.057*
C9	0.2388 (3)	0.11894 (13)	0.9001 (2)	0.0515 (6)
H9A	0.1337	0.1022	0.9098	0.062*
H9B	0.2926	0.0783	0.8703	0.062*
C10	0.3383 (3)	0.14333 (14)	1.0237 (2)	0.0503 (6)
H10	0.2900	0.1882	1.0472	0.060*
C11	0.5130 (3)	0.20529 (12)	0.86732 (19)	0.0450 (5)
C12	0.3528 (3)	0.08930 (16)	1.1284 (2)	0.0611 (7)
C13	0.4089 (4)	0.1153 (2)	1.2489 (3)	0.0852 (10)
H13	0.4389	0.1640	1.2616	0.102*
C14	0.4202 (5)	0.0698 (3)	1.3481 (3)	0.1091 (15)
H14	0.4570	0.0873	1.4279	0.131*
C15	0.3759 (5)	−0.0027 (3)	1.3278 (4)	0.1068 (14)
H15	0.3872	−0.0342	1.3946	0.128*
C16	0.3156 (7)	−0.0287 (2)	1.2108 (4)	0.1208 (16)
H16	0.2835	−0.0771	1.1985	0.145*
C17	0.3031 (6)	0.01876 (19)	1.1100 (3)	0.1013 (13)
H17	0.2607	0.0020	1.0305	0.122*
Cl1	0.47385 (8)	0.26700 (5)	0.54600 (6)	0.0657 (3)
N1	0.3715 (2)	0.20775 (11)	0.78919 (18)	0.0482 (5)
H1A	0.370 (4)	0.2314 (17)	0.719 (3)	0.072*
N2	0.6421 (3)	0.23294 (14)	0.8372 (2)	0.0578 (6)
H2D	0.630 (4)	0.2502 (17)	0.763 (3)	0.069*
H2C	0.729 (4)	0.2361 (16)	0.892 (3)	0.069*
O1	−0.1827 (3)	0.10034 (15)	0.3452 (2)	0.1001 (9)
S1	0.54606 (8)	0.16402 (4)	1.01166 (5)	0.0545 (2)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0405 (11)	0.0522 (13)	0.0481 (12)	0.0008 (9)	0.0097 (9)	0.0073 (10)
C2	0.0428 (13)	0.0599 (15)	0.0759 (17)	0.0002 (11)	0.0155 (12)	0.0020 (12)
C3	0.0397 (13)	0.0679 (17)	0.094 (2)	−0.0023 (12)	−0.0027 (13)	0.0037 (16)
C4	0.0568 (15)	0.0593 (16)	0.0684 (17)	−0.0120 (12)	−0.0090 (13)	0.0069 (13)
C5	0.0608 (16)	0.0835 (19)	0.0547 (14)	−0.0029 (14)	0.0079 (12)	−0.0102 (14)
C6	0.0426 (13)	0.0855 (19)	0.0540 (14)	0.0044 (12)	0.0050 (10)	−0.0087 (13)
C7	0.144 (4)	0.089 (3)	0.069 (2)	−0.015 (2)	−0.030 (2)	−0.0133 (19)
C8	0.0443 (12)	0.0542 (13)	0.0450 (11)	0.0024 (10)	0.0126 (9)	0.0009 (10)
C9	0.0552 (14)	0.0542 (13)	0.0479 (12)	0.0000 (11)	0.0172 (10)	0.0037 (10)
C10	0.0540 (14)	0.0564 (14)	0.0442 (12)	0.0092 (11)	0.0190 (10)	0.0042 (10)
C11	0.0483 (12)	0.0490 (12)	0.0388 (10)	0.0034 (9)	0.0120 (9)	−0.0026 (9)
C12	0.0631 (16)	0.0752 (18)	0.0516 (13)	0.0158 (13)	0.0264 (12)	0.0149 (13)
C13	0.075 (2)	0.121 (3)	0.0552 (16)	−0.0233 (19)	0.0050 (14)	0.0215 (17)
C14	0.091 (3)	0.165 (4)	0.065 (2)	−0.029 (3)	0.0038 (18)	0.041 (2)
C15	0.111 (3)	0.131 (3)	0.082 (2)	0.024 (3)	0.030 (2)	0.056 (2)
C16	0.193 (5)	0.077 (2)	0.114 (3)	0.029 (3)	0.081 (3)	0.028 (2)
C17	0.183 (4)	0.068 (2)	0.0658 (18)	0.017 (2)	0.055 (2)	0.0091 (16)
Cl1	0.0469 (4)	0.1019 (6)	0.0482 (4)	−0.0092 (3)	0.0106 (3)	0.0103 (3)
N1	0.0471 (11)	0.0553 (11)	0.0413 (10)	−0.0030 (8)	0.0080 (8)	0.0062 (8)
N2	0.0464 (12)	0.0820 (16)	0.0438 (11)	−0.0053 (11)	0.0078 (9)	0.0043 (11)
O1	0.0846 (17)	0.1022 (18)	0.0880 (16)	−0.0109 (13)	−0.0347 (13)	−0.0072 (14)
S1	0.0502 (4)	0.0734 (5)	0.0401 (3)	0.0089 (3)	0.0106 (3)	0.0058 (3)

Geometric parameters (Å, º)

C1—C6	1.372 (4)	C9—H9B	0.97
C1—C2	1.380 (3)	C10—C12	1.514 (3)
C1—C8	1.513 (3)	C10—S1	1.834 (3)
C2—C3	1.375 (4)	C10—H10	0.98
C2—H2	0.93	C11—N1	1.314 (3)
C3—C4	1.366 (5)	C11—N2	1.316 (3)
C3—H3	0.93	C11—S1	1.741 (2)
C4—O1	1.371 (3)	C12—C17	1.362 (5)
C4—C5	1.372 (4)	C12—C13	1.402 (4)
C5—C6	1.386 (4)	C13—C14	1.370 (5)
C5—H5	0.93	C13—H13	0.93
C6—H6	0.93	C14—C15	1.386 (7)
C7—O1	1.407 (5)	C14—H14	0.93
C7—H7A	0.96	C15—C16	1.373 (6)
C7—H7B	0.96	C15—H15	0.93
C7—H7C	0.96	C16—C17	1.405 (5)
C8—N1	1.465 (3)	C16—H16	0.93
C8—C9	1.519 (3)	C17—H17	0.93
C8—H8	0.98	N1—H1A	0.89 (3)
C9—C10	1.510 (3)	N2—H2D	0.86 (3)
C9—H9A	0.97	N2—H2C	0.84 (4)
C6—C1—C2	117.7 (2)	C9—C10—C12	116.1 (2)
C6—C1—C8	122.1 (2)	C9—C10—S1	110.06 (15)
C2—C1—C8	120.2 (2)	C12—C10—S1	106.17 (17)
C3—C2—C1	121.2 (3)	C9—C10—H10	108.1
C3—C2—H2	119.4	C12—C10—H10	108.1
C1—C2—H2	119.4	S1—C10—H10	108.1
C4—C3—C2	120.5 (3)	N1—C11—N2	120.3 (2)
C4—C3—H3	119.7	N1—C11—S1	124.04 (18)
C2—C3—H3	119.7	N2—C11—S1	115.60 (18)
C3—C4—O1	116.8 (3)	C17—C12—C13	119.6 (3)
C3—C4—C5	119.4 (3)	C17—C12—C10	122.5 (3)
O1—C4—C5	123.8 (3)	C13—C12—C10	117.7 (3)
C4—C5—C6	119.7 (3)	C14—C13—C12	120.7 (4)
C4—C5—H5	120.1	C14—C13—H13	119.6
C6—C5—H5	120.1	C12—C13—H13	119.6
C1—C6—C5	121.5 (2)	C13—C14—C15	119.0 (4)
C1—C6—H6	119.2	C13—C14—H14	120.5
C5—C6—H6	119.2	C15—C14—H14	120.5
O1—C7—H7A	109.5	C16—C15—C14	121.2 (3)
O1—C7—H7B	109.5	C16—C15—H15	119.4
H7A—C7—H7B	109.5	C14—C15—H15	119.4
O1—C7—H7C	109.5	C15—C16—C17	119.1 (4)
H7A—C7—H7C	109.5	C15—C16—H16	120.4
H7B—C7—H7C	109.5	C17—C16—H16	120.4
N1—C8—C1	109.66 (18)	C12—C17—C16	120.2 (4)
N1—C8—C9	111.24 (19)	C12—C17—H17	119.9
C1—C8—C9	111.7 (2)	C16—C17—H17	119.9
N1—C8—H8	108.1	C11—N1—C8	128.1 (2)
C1—C8—H8	108.1	C11—N1—H1A	115 (2)
C9—C8—H8	108.1	C8—N1—H1A	117 (2)
C10—C9—C8	111.6 (2)	C11—N2—H2D	117 (2)
C10—C9—H9A	109.3	C11—N2—H2C	119 (2)
C8—C9—H9A	109.3	H2D—N2—H2C	124 (3)
C10—C9—H9B	109.3	C4—O1—C7	118.3 (3)
C8—C9—H9B	109.3	C11—S1—C10	101.48 (11)
H9A—C9—H9B	108.0
C6—C1—C2—C3	−1.8 (4)	C9—C10—C12—C13	−164.8 (3)
C8—C1—C2—C3	178.7 (2)	S1—C10—C12—C13	72.5 (3)
C1—C2—C3—C4	0.6 (4)	C17—C12—C13—C14	2.5 (5)
C2—C3—C4—O1	−177.4 (3)	C10—C12—C13—C14	178.0 (3)
C2—C3—C4—C5	1.1 (4)	C12—C13—C14—C15	0.3 (6)
C3—C4—C5—C6	−1.7 (4)	C13—C14—C15—C16	−2.5 (7)
O1—C4—C5—C6	176.7 (3)	C14—C15—C16—C17	1.8 (7)
C2—C1—C6—C5	1.2 (4)	C13—C12—C17—C16	−3.2 (6)
C8—C1—C6—C5	−179.3 (2)	C10—C12—C17—C16	−178.5 (3)
C4—C5—C6—C1	0.5 (5)	C15—C16—C17—C12	1.1 (7)
C6—C1—C8—N1	40.5 (3)	N2—C11—N1—C8	−179.9 (2)
C2—C1—C8—N1	−140.0 (2)	S1—C11—N1—C8	2.4 (3)
C6—C1—C8—C9	−83.2 (3)	C1—C8—N1—C11	−149.2 (2)
C2—C1—C8—C9	96.3 (3)	C9—C8—N1—C11	−25.2 (3)
N1—C8—C9—C10	58.5 (3)	C3—C4—O1—C7	177.6 (3)
C1—C8—C9—C10	−178.66 (19)	C5—C4—O1—C7	−0.8 (5)
C8—C9—C10—C12	173.1 (2)	N1—C11—S1—C10	−8.4 (2)
C8—C9—C10—S1	−66.3 (2)	N2—C11—S1—C10	173.75 (19)
C9—C10—C12—C17	10.5 (4)	C9—C10—S1—C11	38.43 (19)
S1—C10—C12—C17	−112.1 (3)	C12—C10—S1—C11	164.80 (17)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C10—H10···Cl1^i	0.98	2.80	3.555 (2)	135
N2—H2C···Cl1^ii	0.84 (4)	2.38 (4)	3.219 (3)	175 (3)
N1—H1A···Cl1	0.89 (3)	2.38 (3)	3.212 (2)	155 (3)
N2—H2D···Cl1	0.87 (3)	2.50 (3)	3.295 (2)	153 (3)

Symmetry codes: (i) x−1/2, −y+1/2, z+1/2; (ii) x+1/2, −y+1/2, z+1/2.