(6aS,11aR,11cS)-8-Sulfanylidene-2,3,5,6,6a,7,11,11a,11b,11c-decahydro-3a,7a-diaza-1H,4H-benzo[de]anthracen-3a-ium chloride hemihydrate

Abstract

The title compound, C₁₅H₂₃N₂S⁺·Cl⁻·0.5H₂O, was prepared from (6aS,11aR,11cS)-2,3,5,6,6a,7,11,11a,11b,11c-deca­hydro-3a,7a-diaza-1H,4H-benzo[de]anthracene-8-one (sophocarpine) and Lawesson’s reagent. The thione-substituted ring is in an envelope conformation and the three other six-membered rings are in chair conformations. In the crystal, anions and cations are linked by N—H⋯Cl and weak C—H⋯Cl hydrogen bonds. One 0.5-occupancy solvent water mol­ecule lies on a twofold rotation axis and another 0.25-occupancy solvent water mol­ecule is in a general position. The H atoms of these water mol­ecules were not located or included in the refinement.

Related literature

For background to the medicinal uses of sophocarpine natural products, see: Gao et al. (2009 ▶); Jiang et al. (2007 ▶); Liu et al. (2007 ▶). For related structures, see: Ding et al. (2005 ▶); Khan et al. (1992 ▶). For the synthesis, see: Kaleta et al. (2006 ▶).

Experimental

Crystal data

• C₁₅H₂₃N₂S⁺·Cl⁻·0.5H₂O

• M _r = 306.87

• Tetragonal,

• a = 7.793 (5) Å

• c = 52.59 (5) Å

• V = 3194 (4) ų

• Z = 8

• Mo Kα radiation

• μ = 0.36 mm⁻¹

• T = 293 K

• 0.25 × 0.20 × 0.18 mm

Data collection

• Bruker SMART CCD diffractometer

• Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.915, T _max = 0.937

• 11100 measured reflections

• 2816 independent reflections

• 2489 reflections with I > 2σ(I)

• R _int = 0.043

Refinement

• R[F ² > 2σ(F ²)] = 0.071

• wR(F ²) = 0.204

• S = 1.23

• 2816 reflections

• 190 parameters

• H atoms treated by a mixture of independent and constrained refinement

• Δρ_max = 0.64 e Å⁻³

• Δρ_min = −0.25 e Å⁻³

• Absolute structure: Flack (1983 ▶), 1023 Friedel pairs

• Flack parameter: 0.1 (2)

Data collection: SMART (Bruker, 1997 ▶); cell refinement: SAINT (Bruker, 1997 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯Cl1	1.10 (9)	2.01 (8)	3.019 (6)	151 (6)
C4—H4A⋯Cl1i	0.97	2.82	3.726 (7)	155

Symmetry code: (i) .

supplementary crystallographic information

Comment

Sophocarpine ((6aS,11aR,11cS)-2,3,5,6,6a,7,11,11a,11b,11c- decahydro-1H,4H -3a,7a-diaza-βenzo[de] anthracene-8-one) and its derivatives have been found to possess a variety of pharmacological effects (Jiang et al., 2007), including anti-inflammation (Liu et al., 2007) and immunity-regulation activity (Gao et al. 2009). As part of our ongoing investigation of sophocarpine and its derivatives, we report here the crystal structure of the title compound.

The molecular structure of the title compound is shown in Fig. 1. The bond lengths and angles are comparable to related structures (Khan et al., 1992; Ding et al., 2005). The C1/C2/C3/C4/C5/N2 ring is in an envelope conformation with C5 forming the flap. The three other six-membered rings A(N1/C6/C7/C8/C9/C14), B(N1/C10/C11/C12/C13/C14) and C(N2/C1/C2/C3/C4/C5) are in chair conformations. In the crystal, anions and cations are linked by N—H···Cl and weak C—H···Cl hydrogen bonds.

Experimental

The synthetic procedure followed the methods of Kaleta et al. (2006). (6aS,11aR,11cS)-2,3,5,6,6a,7,11,11a,11b,11c-decahydro-1H, 4H-3a,7a-diaza-benzo[de] anthracene-8-one (0.01 mol) and Lawesson's reagent (0.04 mol) were mixed in toluene (100 ml) and stirred under reflux for 2 h. TLC showed that the reaction was completed. The mixture was concentrated and the residue was purified by a silica gel column. The products were stirred in dichloromethane and HCl was added. The resulting crystals were filtered and dried at room temperature. Single crystals suitable for X-ray measurements were obtained by recrystallization of a solution of the title compound in H₂O at room temperature.

Refinement

H atoms bonded to C atoms were fixed geometrically and allowed to ride on their attached atoms, with C—H distances in the range 0.93–0.98Å and with U_iso(H) = 1.2U_eq(C). The H atom bonded to N was refined independently with an isotropic displacement parameter. The H atoms of the partially occupied water molecules could not be located and are not included in the refinement although they are included in the formula.

Figures

Fig. 1.

The molecular structure of the title compound with the atom-labeling scheme. Displacement ellipsoids are drawn at the 30% probability level.

Crystal data

C15H23N2S+·Cl−·0.5H2O	Dx = 1.281 Mg m−3
Mr = 306.87	Mo Kα radiation, λ = 0.71073 Å
Tetragonal, P41212	Cell parameters from 927 reflections
Hall symbol: P 4abw 2nw	θ = 2.7–24.0°
a = 7.793 (5) Å	µ = 0.36 mm−1
c = 52.59 (5) Å	T = 293 K
V = 3194 (4) Å3	Block, yellow
Z = 8	0.25 × 0.20 × 0.18 mm
F(000) = 1320

Data collection

Bruker SMART CCD diffractometer	2816 independent reflections
Radiation source: fine-focus sealed tube	2489 reflections with I > 2σ(I)
graphite	Rint = 0.043
φ and ω scans	θmax = 25.0°, θmin = 2.6°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −9→7
Tmin = 0.915, Tmax = 0.937	k = −7→9
11100 measured reflections	l = −54→62

Refinement

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)] = 0.071	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.204	w = 1/[σ2(Fo2) + (0.104P)2 + 2.0841P] where P = (Fo2 + 2Fc2)/3
S = 1.23	(Δ/σ)max = 0.002
2816 reflections	Δρmax = 0.64 e Å−3
190 parameters	Δρmin = −0.25 e Å−3
0 restraints	Absolute structure: Flack (1983), 1023 Friedel pairs
Primary atom site location: structure-invariant direct methods	Flack parameter: 0.1 (2)

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	Occ. (<1)
S1	0.6279 (2)	0.2217 (2)	0.11342 (2)	0.0559 (4)
Cl1	0.2534 (2)	0.6515 (3)	0.01987 (3)	0.0785 (6)
N1	0.4499 (5)	0.8604 (6)	0.05841 (7)	0.0415 (9)
N2	0.6084 (5)	0.4228 (5)	0.07265 (6)	0.0357 (9)
C1	0.7029 (6)	0.3215 (6)	0.08746 (8)	0.0400 (11)
C2	0.8817 (7)	0.2948 (7)	0.08006 (9)	0.0511 (12)
H2A	0.9548	0.2386	0.0913	0.061*
C3	0.9422 (7)	0.3467 (8)	0.05836 (10)	0.0543 (13)
H3A	1.0566	0.3260	0.0544	0.065*
C4	0.8319 (7)	0.4387 (7)	0.03976 (9)	0.0483 (13)
H4A	0.7864	0.3570	0.0276	0.058*
H4B	0.9011	0.5211	0.0305	0.058*
C5	0.6831 (6)	0.5324 (6)	0.05266 (7)	0.0354 (10)
H5A	0.5944	0.5540	0.0398	0.043*
C6	0.7298 (6)	0.7046 (6)	0.06520 (7)	0.0352 (10)
H6A	0.8128	0.6796	0.0787	0.042*
C7	0.8144 (7)	0.8338 (7)	0.04731 (10)	0.0482 (12)
H7A	0.8599	0.9285	0.0572	0.058*
H7B	0.9096	0.7789	0.0387	0.058*
C8	0.6899 (7)	0.9026 (7)	0.02780 (10)	0.0537 (13)
H8A	0.6499	0.8097	0.0170	0.064*
H8B	0.7472	0.9864	0.0171	0.064*
C9	0.5388 (7)	0.9856 (7)	0.04105 (10)	0.0557 (14)
H9A	0.5785	1.0832	0.0509	0.067*
H9B	0.4580	1.0271	0.0284	0.067*
C10	0.2988 (7)	0.9449 (8)	0.07086 (11)	0.0562 (15)
H10A	0.3382	1.0390	0.0814	0.067*
H10B	0.2236	0.9916	0.0579	0.067*
C11	0.2019 (7)	0.8205 (8)	0.08673 (10)	0.0558 (14)
H11A	0.1539	0.7319	0.0759	0.067*
H11B	0.1076	0.8793	0.0950	0.067*
C12	0.3168 (7)	0.7373 (8)	0.10691 (10)	0.0562 (14)
H12A	0.3504	0.8233	0.1193	0.067*
H12B	0.2523	0.6490	0.1157	0.067*
C13	0.4772 (6)	0.6578 (7)	0.09521 (8)	0.0422 (11)
H13A	0.5549	0.6309	0.1093	0.051*
C14	0.5717 (6)	0.7830 (6)	0.07802 (8)	0.0382 (11)
H14A	0.6122	0.8773	0.0888	0.046*
C15	0.4427 (6)	0.4900 (7)	0.08132 (8)	0.0394 (11)
H15A	0.3878	0.4086	0.0926	0.047*
H15B	0.3676	0.5098	0.0669	0.047*
O1	0.2960 (17)	0.2869 (17)	0.0131 (3)	0.049 (3)	0.25
O2	0.0693 (14)	0.0693 (14)	0.0000	0.179 (12)	0.50
H1	0.390 (8)	0.755 (8)	0.0486 (10)	0.066 (17)*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
S1	0.0630 (9)	0.0610 (9)	0.0436 (6)	0.0009 (7)	−0.0016 (6)	0.0180 (6)
Cl1	0.0562 (9)	0.1312 (17)	0.0481 (7)	−0.0121 (10)	−0.0120 (7)	−0.0032 (8)
N1	0.044 (2)	0.041 (2)	0.0398 (19)	0.0012 (19)	−0.0050 (17)	0.0082 (18)
N2	0.037 (2)	0.040 (2)	0.0303 (17)	−0.0046 (17)	−0.0017 (15)	0.0024 (15)
C1	0.046 (3)	0.037 (3)	0.037 (2)	0.001 (2)	−0.006 (2)	−0.0013 (19)
C2	0.047 (3)	0.057 (3)	0.049 (3)	0.005 (3)	−0.007 (2)	0.007 (2)
C3	0.046 (3)	0.062 (4)	0.055 (3)	0.014 (3)	0.010 (2)	−0.001 (3)
C4	0.054 (3)	0.055 (3)	0.036 (2)	−0.002 (3)	0.008 (2)	−0.002 (2)
C5	0.034 (2)	0.046 (3)	0.0256 (19)	0.000 (2)	−0.0053 (17)	0.0039 (18)
C6	0.028 (2)	0.045 (3)	0.033 (2)	0.001 (2)	−0.0038 (17)	−0.0006 (19)
C7	0.041 (3)	0.048 (3)	0.056 (3)	−0.004 (2)	0.003 (2)	0.007 (2)
C8	0.056 (3)	0.052 (3)	0.052 (3)	−0.006 (3)	0.006 (2)	0.018 (2)
C9	0.056 (4)	0.048 (3)	0.064 (3)	0.002 (3)	0.000 (3)	0.021 (3)
C10	0.047 (3)	0.059 (3)	0.062 (3)	0.020 (3)	0.002 (3)	0.001 (3)
C11	0.044 (3)	0.074 (4)	0.049 (3)	0.013 (3)	0.011 (2)	0.008 (3)
C12	0.049 (3)	0.072 (4)	0.047 (3)	0.011 (3)	0.009 (2)	0.008 (3)
C13	0.038 (3)	0.056 (3)	0.032 (2)	0.003 (2)	−0.0029 (18)	0.007 (2)
C14	0.042 (3)	0.045 (3)	0.0281 (19)	0.000 (2)	−0.0086 (18)	−0.0039 (19)
C15	0.029 (2)	0.049 (3)	0.040 (2)	−0.001 (2)	−0.0022 (19)	0.012 (2)
O1	0.033 (7)	0.026 (7)	0.089 (9)	−0.006 (6)	0.007 (7)	0.002 (6)
O2	0.074 (7)	0.074 (7)	0.39 (3)	−0.027 (9)	0.080 (13)	−0.080 (13)

Geometric parameters (Å, °)

S1—C1	1.676 (5)	C7—H7B	0.9700
N1—C10	1.499 (7)	C8—C9	1.513 (8)
N1—C9	1.505 (6)	C8—H8A	0.9700
N1—C14	1.526 (6)	C8—H8B	0.9700
N1—H1	1.07 (6)	C9—H9A	0.9700
N2—C1	1.331 (6)	C9—H9B	0.9700
N2—C15	1.466 (6)	C10—C11	1.485 (8)
N2—C5	1.474 (5)	C10—H10A	0.9700
C1—C2	1.462 (8)	C10—H10B	0.9700
C2—C3	1.299 (7)	C11—C12	1.532 (7)
C2—H2A	0.9300	C11—H11A	0.9700
C3—C4	1.486 (8)	C11—H11B	0.9700
C3—H3A	0.9300	C12—C13	1.525 (7)
C4—C5	1.529 (7)	C12—H12A	0.9700
C4—H4A	0.9700	C12—H12B	0.9700
C4—H4B	0.9700	C13—C14	1.520 (6)
C5—C6	1.539 (6)	C13—C15	1.522 (7)
C5—H5A	0.9800	C13—H13A	0.9800
C6—C7	1.527 (6)	C14—H14A	0.9800
C6—C14	1.531 (6)	C15—H15A	0.9700
C6—H6A	0.9800	C15—H15B	0.9700
C7—C8	1.511 (7)	O1—O1i	1.38 (3)
C7—H7A	0.9700
C10—N1—C9	110.0 (4)	C7—C8—H8B	109.7
C10—N1—C14	111.5 (4)	C9—C8—H8B	109.7
C9—N1—C14	112.3 (4)	H8A—C8—H8B	108.2
C10—N1—H1	102 (3)	N1—C9—C8	111.1 (4)
C9—N1—H1	114 (3)	N1—C9—H9A	109.4
C14—N1—H1	107 (3)	C8—C9—H9A	109.4
C1—N2—C15	121.2 (4)	N1—C9—H9B	109.4
C1—N2—C5	122.8 (4)	C8—C9—H9B	109.4
C15—N2—C5	111.2 (4)	H9A—C9—H9B	108.0
N2—C1—C2	117.2 (4)	C11—C10—N1	111.0 (4)
N2—C1—S1	123.9 (4)	C11—C10—H10A	109.4
C2—C1—S1	118.9 (4)	N1—C10—H10A	109.4
C3—C2—C1	122.3 (5)	C11—C10—H10B	109.4
C3—C2—H2A	118.8	N1—C10—H10B	109.4
C1—C2—H2A	118.8	H10A—C10—H10B	108.0
C2—C3—C4	121.2 (5)	C10—C11—C12	111.6 (5)
C2—C3—H3A	119.4	C10—C11—H11A	109.3
C4—C3—H3A	119.4	C12—C11—H11A	109.3
C3—C4—C5	112.1 (4)	C10—C11—H11B	109.3
C3—C4—H4A	109.2	C12—C11—H11B	109.3
C5—C4—H4A	109.2	H11A—C11—H11B	108.0
C3—C4—H4B	109.2	C13—C12—C11	111.8 (4)
C5—C4—H4B	109.2	C13—C12—H12A	109.3
H4A—C4—H4B	107.9	C11—C12—H12A	109.3
N2—C5—C4	109.8 (4)	C13—C12—H12B	109.3
N2—C5—C6	107.0 (3)	C11—C12—H12B	109.3
C4—C5—C6	115.3 (4)	H12A—C12—H12B	107.9
N2—C5—H5A	108.2	C14—C13—C15	110.6 (3)
C4—C5—H5A	108.2	C14—C13—C12	112.1 (4)
C6—C5—H5A	108.2	C15—C13—C12	113.5 (4)
C7—C6—C14	110.8 (4)	C14—C13—H13A	106.7
C7—C6—C5	114.4 (4)	C15—C13—H13A	106.7
C14—C6—C5	110.3 (4)	C12—C13—H13A	106.7
C7—C6—H6A	107.0	C13—C14—N1	110.7 (4)
C14—C6—H6A	107.0	C13—C14—C6	113.3 (4)
C5—C6—H6A	107.0	N1—C14—C6	111.1 (3)
C8—C7—C6	112.0 (4)	C13—C14—H14A	107.1
C8—C7—H7A	109.2	N1—C14—H14A	107.1
C6—C7—H7A	109.2	C6—C14—H14A	107.1
C8—C7—H7B	109.2	N2—C15—C13	107.5 (4)
C6—C7—H7B	109.2	N2—C15—H15A	110.2
H7A—C7—H7B	107.9	C13—C15—H15A	110.2
C7—C8—C9	109.8 (4)	N2—C15—H15B	110.2
C7—C8—H8A	109.7	C13—C15—H15B	110.2
C9—C8—H8A	109.7	H15A—C15—H15B	108.5

Symmetry codes: (i) y, x, −z.

Hydrogen-bond geometry (Å, °)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···Cl1	1.10 (9)	2.01 (8)	3.019 (6)	151 (6)
C4—H4A···Cl1i	0.97	2.82	3.726 (7)	155

Symmetry codes: (i) y, x, −z.