Azinyl sulfides. L. 14-Methyl-1,4-thia­zino­[2,3-c;6,5-c']­di­quinoline

The title compound, C₁₉H₁₃N₃S, is folded, with the central ring in a boat conformation. The folding angle between the two quinoline rings is 150.2 (1)°. The 14-methyl substituent is in a quasi-axial orientation with respect to the thia­zine ring. The S...N-C_methyl angle is 120.1 (1)°.

S1. Comment

Quinolines condensed with certain heterocycles have recently become important compounds because of their affinity to the benzodiazepine receptors (Moreau et al., 1988; Anzini et al., 1990). On the other hand, tricyclic phenothiazines and azaphenothiazines constitute a major class of pharmaceutical agents with beneficial antipsychotic, CNR depressant and antihistaminic properties (Byck, 1975; Reynolds, 1989; Horn, 1990). These compounds are of interest in determining the constitution (synthesis with or without the Smiles rearrangement stage) and the effects of the nature and position of the substituents on the conformation and configuration (a rigid orientation of the 10-substituent) of the tricyclic ring system, and on the pharmaceutical activity (Sainsbury, 1978; Andreetti et al., 1980; de Meester et al., 1985; Baranski et al., 1990). The purpose of this study of 14-methyl-1,4-thiazino[2,3 - c;6,5 - c']diquinoline, (I), is to determine the effect of two additional benzene rings on the configuration and conformation of pentacyclic dibenzoazaphenothiazine and to compare the results with the structures of the related tricyclic phenothiazines, (II)-(IV). \scheme

The configuration of the molecule of (I) and the atom-numbering scheme are shown in the ORTEPII (Johnson, 1976) drawing in Fig. 1. The molecule as a whole is not planar and the butterfly angle between two quinoline planes is 150.2 (1)°. The central thiazine ring has a boat conformation, with N3 and S1 0.352 (1) and 0.519 (1) Å, respectively, out of the basal plane formed by C3, C4, C13 and C14. The dihedral angle between the planes determined by the atoms of the two halves of the thiazine ring (i.e. S1/C3/C4/N3 and S1/C13/C14/N3) is 142.8 (7)°.

The thiazine nitrogen atom N3 shows pyramidality. It is worth noting that the quinoline rings are non-planar, with dihedral angles between the pyridine and benzene rings of 3.5 (1) and 3.7 (1)°, respectively.

Selected bond lengths and angles are given in Table 1. Whereas the N3—C4 and N3—C14 bond lengths are very similar to those found in other N-methylphenothiazine and N-methylazaphenothiazines, (II)-(IV), the N3—CH₃ bond lengths are different regardless of the type of aromatic ring or the C—N—C and dihedral angles [1.474 (2) versus 1.455 in (II), 1.490 in (III) and 1.385 Å in (IV)]. The C3—S1—C13 and C4—N3—C14 bond angles do not differ from the values found in the tricyclic N-methylarenothiazines (II)-(IV) (Andreetti et al., 1974, 1980; Chu & van der Helm, 1974).

The most unexpected molecular feature of (I) is the orientation of the methyl substituent. In contrast to all known N-substituted phenothiazines and azaphenothiazines, the methyl substituent is in a quasi-axial orientation with the respect to the thiazine ring, with torsion angles C3—C4—N3—C21 and C13—C14—N3—C21 of -114.1 (2) and 113.2 (2)°, respectively. The S···N—CH₃ angle is 120.1 (1)°, which is significantly smaller than values found in N-methylarenothiazines (153.7–168.1°; Andreetti et al., 1974, 1980; Chu & van der Helm, 1974).

There are very close contacts between the methyl group and the H6 and H16 atoms. The C21···H6 and C21···H16 distances are 2.76 Å, which is less than the sum the van der Waals radii of the CH₃ and H atoms (3.20 Å; Pauling, 1960). These steric interactions cause deshielding of the H6, H16 and CH₃ protons, as shown in the ¹H NMR spectrum by values of 0.26–0.38 p.p.m., in comparison with the analogous protons in the 4-methylaminoquinoline derivatives (Maślankiewicz & Skrzypek, 1994; Skrzypek 1997).

S2. Experimental

Compound (I) was synthesized and purified as previously reported by Pluta (1997). Single crystals suitable for X-ray data collection were obtained on slow evaporation from an N,N-dimethylformamide solution.

S3. Refinement

Please provide details of H-atom refinement

Computing details

Data collection: CAD-4 Software (Enraf-Nonius, 1989); cell refinement: CAD-4 Software; data reduction: SDP-Plus (Frenz, 1985); program(s) used to solve structure: SHELXS86 (Sheldrick, 1990); program(s) used to refine structure: SHELXL93 (Sheldrick, 1993); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL93.

Figures

Fig. 1. An ORTEPII (Johnson, 1976) view of the molecule of compound (I) with 50% probability displacement ellipsoids. H atoms are drawn as small spheres of arbitrary radii.

4-methyl-1,4-thiazino[2,3 - c;6,5 - c']diquinoline

Crystal data

C19H13N3S	F(000) = 656
Mr = 315.38	Dx = 1.379 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 11.848 (3) Å	Cell parameters from 25 reflections
b = 11.015 (4) Å	θ = 6–14°
c = 12.313 (4) Å	µ = 0.22 mm^−1
β = 109.01 (3)°	T = 293 K
V = 1519.3 (8) Å^3	Prism, yellow
Z = 4	0.82 × 0.28 × 0.21 mm

Data collection

Enraf-Nonius CAD-4 diffractometer	Rint = 0.021
Radiation source: fine-focus sealed tube	θmax = 30.0°, θmin = 2.6°
Graphite monochromator	h = −16→15
ω/2θ scans	k = 0→15
4597 measured reflections	l = 0→17
4409 independent reflections	3 standard reflections every 60 min
3052 reflections with I > 2σ(I)	intensity decay: 0.5%

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.042	H-atom parameters constrained
wR(F^2) = 0.109	Calculated w = 1/[σ^2(Fo^2) + (0.0681P)^2 + 0.0125P] where P = (Fo^2 + 2Fc^2)/3
S = 1.03	(Δ/σ)max = 0.017
4315 reflections	Δρmax = 0.21 e Å^−3
210 parameters	Δρmin = −0.21 e Å^−3
0 restraints	Extinction correction: SHELXL93 (Sheldrick, 1993), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0118 (18)

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 on F² for ALL reflections except for 94 with very negative F² or flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The observed criterion of F² > σ(F²) is used only for calculating _R_factor_obs 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
S1	0.54501 (3)	0.05215 (4)	0.33123 (3)	0.05108 (13)
N1	0.80594 (13)	−0.01535 (14)	0.62556 (10)	0.0587 (4)
C2	0.7106 (2)	0.0264 (2)	0.54601 (13)	0.0551 (4)
H2	0.6582 (2)	0.0749 (2)	0.56896 (13)	0.066*
C3	0.68292 (13)	0.00164 (13)	0.42723 (11)	0.0439 (3)
C4	0.76053 (12)	−0.06552 (11)	0.39000 (11)	0.0387 (3)
C5	0.86893 (12)	−0.10646 (12)	0.47304 (11)	0.0418 (3)
C6	0.96006 (13)	−0.16755 (13)	0.44433 (13)	0.0492 (3)
H6	0.95199 (13)	−0.18062 (13)	0.36754 (13)	0.059*
C7	1.06057 (14)	−0.2079 (2)	0.5286 (2)	0.0624 (4)
H7	1.11993 (14)	−0.2482 (2)	0.5086 (2)	0.075*
C8	1.0739 (2)	−0.1886 (2)	0.6443 (2)	0.0686 (5)
H8	1.1408 (2)	−0.2189 (2)	0.7009 (2)	0.082*
C9	0.9903 (2)	−0.1261 (2)	0.67531 (13)	0.0639 (5)
H9	1.0018 (2)	−0.1120 (2)	0.75266 (13)	0.077*
C10	0.88491 (14)	−0.08180 (14)	0.59058 (12)	0.0498 (4)
N2	0.55081 (11)	0.17115 (12)	0.02745 (11)	0.0536 (3)
C12	0.53170 (13)	0.15748 (14)	0.12578 (13)	0.0506 (3)
H12	0.47616 (13)	0.20822 (14)	0.14139 (13)	0.061*
C13	0.59009 (12)	0.07067 (12)	0.20937 (11)	0.0409 (3)
C14	0.67742 (11)	−0.00166 (11)	0.19243 (10)	0.0367 (3)
C15	0.70708 (12)	0.01556 (12)	0.09039 (10)	0.0389 (3)
C16	0.80041 (14)	−0.04751 (13)	0.06605 (12)	0.0474 (3)
H16	0.84925 (14)	−0.10003 (13)	0.12039 (12)	0.057*
C17	0.8190 (2)	−0.03136 (15)	−0.03730 (14)	0.0557 (4)
H17	0.8807 (2)	−0.07268 (15)	−0.05242 (14)	0.067*
C18	0.7454 (2)	0.04720 (15)	−0.12061 (13)	0.0570 (4)
H18	0.7562 (2)	0.05427 (15)	−0.19184 (13)	0.068*
C19	0.6586 (2)	0.11280 (15)	−0.09785 (12)	0.0538 (4)
H19	0.6126 (2)	0.16659 (15)	−0.15269 (12)	0.065*
C20	0.63747 (13)	0.10032 (13)	0.00836 (11)	0.0434 (3)
N3	0.73816 (11)	−0.09129 (10)	0.27242 (9)	0.0411 (3)
C21	0.71678 (14)	−0.21884 (13)	0.23508 (13)	0.0499 (3)
H21A	0.7034 (10)	−0.2663 (2)	0.2952 (4)	0.075*
H21B	0.7851 (4)	−0.2498 (3)	0.2184 (9)	0.075*
H21C	0.6479 (6)	−0.2235 (2)	0.1673 (6)	0.075*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0445 (2)	0.0682 (3)	0.0445 (2)	0.0081 (2)	0.01990 (15)	0.0018 (2)
N1	0.0678 (9)	0.0762 (9)	0.0328 (6)	−0.0099 (7)	0.0176 (6)	0.0008 (6)
C2	0.0627 (9)	0.0697 (10)	0.0390 (7)	−0.0037 (8)	0.0248 (7)	−0.0031 (7)
C3	0.0473 (7)	0.0510 (8)	0.0356 (6)	−0.0023 (6)	0.0166 (5)	0.0002 (6)
C4	0.0450 (7)	0.0389 (6)	0.0316 (6)	−0.0034 (5)	0.0116 (5)	0.0025 (5)
C5	0.0475 (7)	0.0393 (6)	0.0363 (6)	−0.0054 (6)	0.0103 (5)	0.0065 (5)
C6	0.0489 (7)	0.0446 (7)	0.0495 (8)	0.0006 (6)	0.0095 (6)	0.0067 (6)
C7	0.0484 (8)	0.0542 (9)	0.0745 (11)	0.0035 (7)	0.0061 (8)	0.0110 (8)
C8	0.0549 (9)	0.0650 (10)	0.0662 (11)	−0.0041 (8)	−0.0073 (8)	0.0225 (9)
C9	0.0691 (10)	0.0683 (11)	0.0408 (8)	−0.0165 (9)	−0.0006 (7)	0.0147 (7)
C10	0.0573 (8)	0.0527 (8)	0.0354 (7)	−0.0133 (7)	0.0097 (6)	0.0082 (6)
N2	0.0530 (7)	0.0556 (7)	0.0490 (7)	0.0076 (6)	0.0123 (6)	0.0139 (6)
C12	0.0485 (8)	0.0509 (8)	0.0515 (8)	0.0109 (6)	0.0150 (6)	0.0064 (7)
C13	0.0403 (6)	0.0448 (7)	0.0365 (6)	−0.0005 (5)	0.0109 (5)	0.0003 (5)
C14	0.0402 (6)	0.0362 (6)	0.0307 (6)	−0.0012 (5)	0.0076 (5)	−0.0024 (5)
C15	0.0460 (7)	0.0381 (6)	0.0305 (6)	−0.0046 (5)	0.0095 (5)	−0.0047 (5)
C16	0.0563 (8)	0.0462 (8)	0.0417 (7)	0.0014 (6)	0.0187 (6)	−0.0047 (6)
C17	0.0680 (10)	0.0572 (9)	0.0501 (8)	−0.0076 (7)	0.0306 (8)	−0.0141 (7)
C18	0.0766 (11)	0.0616 (9)	0.0359 (7)	−0.0187 (8)	0.0228 (7)	−0.0072 (7)
C19	0.0672 (9)	0.0554 (9)	0.0340 (7)	−0.0122 (7)	0.0099 (6)	0.0034 (6)
C20	0.0478 (7)	0.0427 (7)	0.0353 (6)	−0.0082 (6)	0.0074 (5)	0.0010 (5)
N3	0.0518 (6)	0.0377 (5)	0.0317 (5)	0.0042 (5)	0.0104 (5)	−0.0012 (4)
C21	0.0625 (9)	0.0387 (7)	0.0474 (8)	−0.0034 (6)	0.0166 (7)	−0.0033 (6)

Geometric parameters (Å, º)

S1—C13	1.7608 (15)	N2—C12	1.311 (2)
S1—C3	1.766 (2)	N2—C20	1.369 (2)
N1—C2	1.314 (2)	C12—C13	1.410 (2)
N1—C10	1.364 (2)	C13—C14	1.375 (2)
C2—C3	1.417 (2)	C14—N3	1.415 (2)
C3—C4	1.370 (2)	C14—C15	1.423 (2)
C4—N3	1.413 (2)	C15—C16	1.418 (2)
C4—C5	1.429 (2)	C15—C20	1.425 (2)
C5—C6	1.412 (2)	C16—C17	1.372 (2)
C5—C10	1.423 (2)	C17—C18	1.407 (2)
C6—C7	1.374 (2)	C18—C19	1.358 (2)
C7—C8	1.398 (3)	C19—C20	1.416 (2)
C8—C9	1.360 (3)	N3—C21	1.474 (2)
C9—C10	1.427 (2)
C13—S1—C3	97.79 (7)	N2—C12—C13	124.11 (14)
C2—N1—C10	117.66 (13)	C14—C13—C12	119.79 (13)
N1—C2—C3	123.8 (2)	C14—C13—S1	120.96 (10)
C4—C3—C2	119.63 (14)	C12—C13—S1	119.19 (11)
C4—C3—S1	121.44 (10)	C13—C14—N3	122.43 (12)
C2—C3—S1	118.86 (12)	C13—C14—C15	118.12 (12)
C3—C4—N3	121.93 (12)	N3—C14—C15	119.45 (12)
C3—C4—C5	118.39 (12)	C16—C15—C14	123.72 (12)
N3—C4—C5	119.64 (12)	C16—C15—C20	118.84 (12)
C6—C5—C10	119.11 (13)	C14—C15—C20	117.44 (13)
C6—C5—C4	123.61 (12)	C17—C16—C15	120.28 (15)
C10—C5—C4	117.27 (14)	C16—C17—C18	120.5 (2)
C7—C6—C5	120.7 (2)	C19—C18—C17	120.52 (14)
C6—C7—C8	120.2 (2)	C18—C19—C20	120.82 (15)
C9—C8—C7	120.81 (15)	N2—C20—C19	118.12 (13)
C8—C9—C10	120.8 (2)	N2—C20—C15	123.03 (13)
N1—C10—C5	123.09 (14)	C19—C20—C15	118.85 (14)
N1—C10—C9	118.65 (14)	C4—N3—C14	117.15 (11)
C5—C10—C9	118.2 (2)	C4—N3—C21	117.82 (11)
C12—N2—C20	117.24 (12)	C14—N3—C21	116.82 (11)
C10—N1—C2—C3	2.9 (3)	C3—S1—C13—C12	−151.91 (12)
N1—C2—C3—C4	−2.6 (2)	C12—C13—C14—N3	−179.23 (12)
N1—C2—C3—S1	174.30 (13)	S1—C13—C14—N3	−2.1 (2)
C13—S1—C3—C4	−32.09 (13)	C12—C13—C14—C15	0.9 (2)
C13—S1—C3—C2	151.06 (13)	S1—C13—C14—C15	178.10 (10)
C2—C3—C4—N3	−179.04 (13)	C13—C14—C15—C16	175.85 (12)
S1—C3—C4—N3	4.1 (2)	N3—C14—C15—C16	−4.0 (2)
C2—C3—C4—C5	−1.3 (2)	C13—C14—C15—C20	−4.8 (2)
S1—C3—C4—C5	−178.12 (10)	N3—C14—C15—C20	175.35 (11)
C3—C4—C5—C6	−174.63 (13)	C14—C15—C16—C17	176.05 (14)
N3—C4—C5—C6	3.2 (2)	C20—C15—C16—C17	−3.3 (2)
C3—C4—C5—C10	4.4 (2)	C15—C16—C17—C18	−0.4 (2)
N3—C4—C5—C10	−177.79 (12)	C16—C17—C18—C19	3.3 (2)
C10—C5—C6—C7	3.0 (2)	C17—C18—C19—C20	−2.3 (2)
C4—C5—C6—C7	−177.95 (14)	C12—N2—C20—C19	179.35 (14)
C5—C6—C7—C8	−0.1 (2)	C12—N2—C20—C15	−0.9 (2)
C6—C7—C8—C9	−2.4 (3)	C18—C19—C20—N2	178.38 (14)
C7—C8—C9—C10	1.9 (3)	C18—C19—C20—C15	−1.4 (2)
C2—N1—C10—C5	0.6 (2)	C16—C15—C20—N2	−175.61 (13)
C2—N1—C10—C9	178.83 (15)	C14—C15—C20—N2	5.0 (2)
C6—C5—C10—N1	174.85 (14)	C16—C15—C20—C19	4.1 (2)
C4—C5—C10—N1	−4.2 (2)	C14—C15—C20—C19	−175.24 (12)
C6—C5—C10—C9	−3.4 (2)	C3—C4—N3—C14	33.5 (2)
C4—C5—C10—C9	177.51 (13)	C5—C4—N3—C14	−144.23 (12)
C8—C9—C10—N1	−177.4 (2)	C3—C4—N3—C21	−114.07 (15)
C8—C9—C10—C5	1.0 (2)	C5—C4—N3—C21	68.2 (2)
C20—N2—C12—C13	−3.5 (2)	C13—C14—N3—C4	−34.7 (2)
N2—C12—C13—C14	3.5 (2)	C15—C14—N3—C4	145.10 (12)
N2—C12—C13—S1	−173.71 (13)	C13—C14—N3—C21	113.16 (15)
C3—S1—C13—C14	30.91 (12)	C15—C14—N3—C21	−67.0 (2)