4-Phenyl-2-(2-pyridylmethyl­sulfan­yl)-3H-1,5-benzodiazepine

Doubia, M.L.; Bouhfid, R.; Ahabchane, N.H.; Essassi, E.M.; El Ammari, L.

doi:10.1107/S1600536807029376

4-Phenyl-2-(2-pyridylmethylsulfanyl)-3H-1,5-benzodiazepine

M. L. Doubia, R. Bouhfid, N. H. Ahabchane, E. M. Essassi and L. El Ammari

The title compound, C₂₁H₁₇N₃S, is a new heterocyclic system derived from 1,5-benzodiazepine. The molecule is built up from two fused six- and seven-membered rings with phenyl and picolylsulfanyl side groups. The seven-membered ring displays a twist-chair conformation. The cohesion of the crystal structure is ensured by weak slipped π–π stacking between the pyridine rings of symmetry-related molecules [interplanar distance = 3.42 Å and centroid-to-centroid vector = 3.784 (1) Å] and weak C—H

N hydrogen-bond interactions.

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Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807029376/dn2192sup1.cif Contains datablocks I, global
	Structure factor file (CIF format) https://doi.org/10.1107/S1600536807029376/dn2192Isup2.hkl Contains datablock I

CCDC reference: 655028

checkCIF report

Key indicators

Single-crystal X-ray study
T = 296 K
Mean (C-C) = 0.003 Å
R factor = 0.044
wR factor = 0.152
Data-to-parameter ratio = 25.8

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT230_ALERT_2_C Hirshfeld Test Diff for    C11    -   C15     ..       5.70 su
PLAT410_ALERT_2_C Short Intra H...H Contact  H8B    ..  H21     ..       1.98 Ang.
PLAT480_ALERT_4_C Long H...A H-Bond Reported H13    ..  N1      ..       2.67 Ang.

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

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

Comment top

Many benzodiazepines and their derivatives reveal very interesting biological and pharmacological activities (Dourlat et al., 2007, Zellou et al., 1999). Furthermore, it has been shown that the introduction of one or several nitrogenous heterocycles on the different positions of the diazepinic cycle increases the biological activity considerably (Atack et al., 2006, Kumar et al., 2006). In this context, our team has been interested in the synthesis of new heterocyclic systems deriving from 1,5-benzodiazepine (Ghomsi et al., 2004, El Azzaoui et al., 2006).

The 2-(benzylsulfanyl)-4-phenyl-3H-1,5-benzodiazepine (II) (Doubia et al. 2007) and 2-(picolylsulfanyl)-4-phenyl-3H-1,5-benzodiazepine (I) are two almost identical molecules as shown in scheme 1. In fact,each molecule is built up from two fused six-membered and seven-membered rings linked to benzylsulfanyl and phenyl for (II) or picolylsulfanyl and phenyl for (I)(Fig.1). The seven-membered ring displays a twist-chair conformation in both moleclules (I) and (II), as indicated by the total puckering amplitude Q_T=0.859 (2) Å and spherical polar angle θ₂=74.83 (9)° with φ₂=-48.0 (2)° and φ₃=103.0 (4)° for (II) and Q_T=0.860 (2) Å θ₂=74.45 (8)° with φ₂=-48.4 (2)° and φ₃=103.1 (3)° for (I) (Cremer & Pople, 1975). However, slightly geometrical differences exist between the torsion angles of the two molecules, especially: C9—S1—C10—C11 = -87.07°, C8—C7—C17—C22 = 3.36° and C8—C7—C17—C18 =-177.46° in molecule (II) difer from that observed in molecule (I), respectively: -90.23 °, 10.04° and -170.26°. But the most important difference resides in the measurements of the crystal unit cell. This difference can be explained by the intermolecular hydrogen bonds (H···N3) that influence the orientation of the molecules in the crystals. The crystal structure is stabilized by weak C—H···N hydrogen bonds (Table 1)and also by weak slipped π-π stacking between symmetry related molecules (C16 to C21 ring) with interplanar distance of 3.42 Å and centroid to centroid vector of 3.784 (1) Å.

Related literature top

For related literature, see: Atack et al. (2006); Cremer & Pople (1975); Doubia et al. (2007); Dourlat et al. (2007); El Azzaoui et al. (2006); Ghomsi et al. (2004); Kumar et al. (2006); Zellou et al. (1999).

Experimental top

To a solution of 4-phenyl-1,5-benzodiazepine-2-thione (1 g, 3.96 mmol) and benzylbromide (0.70 ml, 4.36 mmol) or picolylchloride (0.51 g, 3.96 mmol) in DMF (20 ml), 0.5 mmol of tetra-n-butylammonium bromide and 4.36 mmol (0.60 g) of anhydrous potassium carbonate were added. After filtration, the solvent was evaporated under reduced pressure and the crude residue was recrystallized from ethanol giving compound II in 76% yield.

Structure description top

Computing details top

Data collection: APEX2 (Bruker, 2005); cell refinement: APEX2; data reduction: APEX2; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top

	Fig. 1. Molecular view of compound (I) with the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are represented as small spheres of arbitrary radii.
	Fig. 2. Schematic representations of the structures of (I) and (II).

4-Phenyl-2-(2-pyridylmethylsulfanyl)-3H-1,5-benzodiazepine top

Crystal data top

C₂₁H₁₇N₃S	F(000) = 720
M_r = 343.44	D_x = 1.310 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -p 2yn	Cell parameters from 5841 reflections
a = 14.2995 (3) Å	θ = 2.8–31.6°
b = 8.7004 (2) Å	µ = 0.19 mm⁻¹
c = 14.3851 (4) Å	T = 296 K
β = 103.337 (1)°	Parallelepiped, pale yellow
V = 1741.40 (7) Å³	0.38 × 0.22 × 0.12 mm
Z = 4

Data collection top

Bruker X8 APEXII KappaCCD area-detector diffractometer	4115 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.027
Graphite monochromator	θ_max = 31.6°, θ_min = 2.8°
φ scans, and ω scans with κ offsets	h = −21→21
25788 measured reflections	k = −12→11
5841 independent reflections	l = −21→21

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.044	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.152	H-atom parameters constrained
S = 1.11	w = 1/[σ²(F_o²) + (0.0656P)² + 0.3072P] where P = (F_o² + 2F_c²)/3
5841 reflections	(Δ/σ)_max = 0.001
226 parameters	Δρ_max = 0.44 e Å⁻³
0 restraints	Δρ_min = −0.23 e Å⁻³

Crystal data top

C₂₁H₁₇N₃S	V = 1741.40 (7) Å³
M_r = 343.44	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 14.2995 (3) Å	µ = 0.19 mm⁻¹
b = 8.7004 (2) Å	T = 296 K
c = 14.3851 (4) Å	0.38 × 0.22 × 0.12 mm
β = 103.337 (1)°

Data collection top

Bruker X8 APEXII KappaCCD area-detector diffractometer	4115 reflections with I > 2σ(I)
25788 measured reflections	R_int = 0.027
5841 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.044	0 restraints
wR(F²) = 0.152	H-atom parameters constrained
S = 1.11	Δρ_max = 0.44 e Å⁻³
5841 reflections	Δρ_min = −0.23 e Å⁻³
226 parameters

Special details top

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 (Å²) top

	x	y	z	U_iso*/U_eq
S1	0.67517 (3)	0.23757 (5)	0.79695 (3)	0.04864 (13)
N1	0.49783 (9)	0.16662 (14)	0.81086 (8)	0.0431 (3)
N2	0.38145 (8)	0.15159 (13)	0.60681 (8)	0.0407 (2)
N3	0.69778 (11)	0.59718 (18)	0.88759 (13)	0.0654 (4)
C1	0.40814 (10)	0.09371 (15)	0.78066 (10)	0.0409 (3)
C2	0.36691 (12)	0.0369 (2)	0.85337 (12)	0.0529 (4)
H2	0.3993	0.0496	0.9168	0.064*
C3	0.27984 (14)	−0.0371 (2)	0.83291 (15)	0.0611 (4)
H3	0.2555	−0.0789	0.8820	0.073*
C4	0.22823 (12)	−0.0495 (2)	0.73931 (14)	0.0592 (4)
H4	0.1695	−0.1004	0.7252	0.071*
C5	0.26406 (11)	0.01364 (19)	0.66732 (12)	0.0509 (3)
H5	0.2272	0.0102	0.6050	0.061*
C6	0.35536 (10)	0.08363 (15)	0.68549 (10)	0.0401 (3)
C7	0.46882 (9)	0.14973 (14)	0.59740 (9)	0.0355 (2)
C8	0.54617 (10)	0.06568 (15)	0.66913 (9)	0.0389 (3)
H8A	0.5260	−0.0386	0.6781	0.047*
H8B	0.6054	0.0618	0.6471	0.047*
C9	0.56080 (9)	0.15465 (14)	0.76107 (9)	0.0379 (3)
C10	0.66896 (12)	0.32930 (18)	0.90820 (11)	0.0504 (3)
H10A	0.6265	0.2700	0.9382	0.060*
H10B	0.7324	0.3278	0.9507	0.060*
C11	0.63335 (10)	0.49434 (17)	0.89685 (9)	0.0442 (3)
C12	0.66942 (17)	0.7437 (2)	0.88149 (18)	0.0729 (6)
H12	0.7137	0.8185	0.8744	0.087*
C13	0.57906 (17)	0.7904 (2)	0.88511 (14)	0.0682 (5)
H13	0.5633	0.8942	0.8829	0.082*
C14	0.51236 (16)	0.6808 (3)	0.89215 (16)	0.0704 (5)
H14	0.4496	0.7083	0.8926	0.085*
C15	0.54042 (14)	0.5277 (2)	0.89861 (13)	0.0597 (4)
H15	0.4972	0.4502	0.9040	0.072*
C16	0.49184 (10)	0.23272 (14)	0.51568 (9)	0.0375 (3)
C17	0.42283 (11)	0.32813 (18)	0.45926 (10)	0.0475 (3)
H17	0.3633	0.3398	0.4742	0.057*
C18	0.44150 (14)	0.4053 (2)	0.38182 (12)	0.0602 (4)
H18	0.3945	0.4671	0.3443	0.072*
C19	0.53019 (16)	0.3904 (2)	0.36022 (12)	0.0637 (5)
H19	0.5433	0.4438	0.3087	0.076*
C20	0.59865 (15)	0.2978 (2)	0.41406 (14)	0.0617 (4)
H20	0.6580	0.2876	0.3986	0.074*
C21	0.58049 (12)	0.21835 (18)	0.49195 (12)	0.0490 (3)
H21	0.6277	0.1555	0.5283	0.059*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.03589 (19)	0.0547 (2)	0.0509 (2)	−0.00153 (14)	0.00101 (15)	−0.00703 (15)
N1	0.0428 (6)	0.0460 (6)	0.0390 (5)	0.0000 (5)	0.0065 (5)	−0.0043 (5)
N2	0.0355 (5)	0.0435 (6)	0.0409 (6)	−0.0012 (4)	0.0041 (4)	0.0013 (4)
N3	0.0542 (8)	0.0557 (8)	0.0854 (11)	0.0004 (7)	0.0145 (8)	−0.0003 (8)
C1	0.0408 (6)	0.0385 (6)	0.0441 (6)	0.0025 (5)	0.0111 (5)	−0.0016 (5)
C2	0.0528 (8)	0.0610 (9)	0.0478 (8)	0.0040 (7)	0.0176 (7)	0.0024 (7)
C3	0.0577 (10)	0.0629 (10)	0.0707 (11)	0.0019 (8)	0.0313 (9)	0.0125 (8)
C4	0.0445 (8)	0.0587 (9)	0.0776 (12)	−0.0074 (7)	0.0204 (8)	0.0048 (8)
C5	0.0403 (7)	0.0546 (8)	0.0558 (9)	−0.0051 (6)	0.0068 (6)	0.0009 (7)
C6	0.0372 (6)	0.0379 (6)	0.0447 (7)	−0.0003 (5)	0.0084 (5)	−0.0004 (5)
C7	0.0353 (6)	0.0347 (5)	0.0340 (5)	−0.0004 (4)	0.0028 (4)	−0.0042 (4)
C8	0.0386 (6)	0.0382 (6)	0.0381 (6)	0.0051 (5)	0.0050 (5)	−0.0020 (5)
C9	0.0369 (6)	0.0355 (5)	0.0374 (6)	0.0027 (4)	0.0009 (5)	−0.0004 (4)
C10	0.0491 (8)	0.0498 (8)	0.0428 (7)	0.0012 (6)	−0.0088 (6)	−0.0035 (6)
C11	0.0421 (7)	0.0517 (7)	0.0333 (6)	0.0009 (6)	−0.0026 (5)	−0.0029 (5)
C12	0.0766 (14)	0.0537 (10)	0.0908 (15)	−0.0020 (9)	0.0245 (12)	0.0067 (9)
C13	0.0884 (15)	0.0552 (9)	0.0604 (10)	0.0209 (10)	0.0163 (10)	0.0067 (8)
C14	0.0641 (11)	0.0749 (12)	0.0742 (12)	0.0199 (10)	0.0199 (9)	0.0035 (10)
C15	0.0538 (9)	0.0651 (10)	0.0602 (10)	0.0003 (8)	0.0130 (8)	0.0002 (8)
C16	0.0398 (6)	0.0368 (6)	0.0340 (6)	−0.0048 (5)	0.0046 (5)	−0.0054 (4)
C17	0.0446 (7)	0.0493 (7)	0.0438 (7)	−0.0062 (6)	0.0003 (6)	0.0046 (6)
C18	0.0683 (11)	0.0607 (9)	0.0443 (8)	−0.0104 (8)	−0.0020 (7)	0.0103 (7)
C19	0.0897 (14)	0.0609 (10)	0.0424 (8)	−0.0158 (9)	0.0194 (8)	0.0021 (7)
C20	0.0710 (11)	0.0592 (9)	0.0649 (10)	−0.0070 (8)	0.0366 (9)	−0.0054 (8)
C21	0.0491 (8)	0.0475 (7)	0.0525 (8)	0.0030 (6)	0.0163 (6)	−0.0025 (6)

Geometric parameters (Å, º) top

S1—C9	1.7527 (14)	C10—C11	1.520 (2)
S1—C10	1.8088 (16)	C10—H10A	0.9700
N1—C9	1.2776 (18)	C10—H10B	0.9700
N1—C1	1.4067 (18)	C11—C15	1.366 (2)
N2—C7	1.2875 (17)	C12—C13	1.367 (3)
N2—C6	1.4016 (17)	C12—H12	0.9300
N3—C11	1.313 (2)	C13—C14	1.369 (3)
N3—C12	1.335 (2)	C13—H13	0.9300
C1—C2	1.404 (2)	C14—C15	1.388 (3)
C1—C6	1.405 (2)	C14—H14	0.9300
C2—C3	1.372 (3)	C15—H15	0.9300
C2—H2	0.9300	C16—C21	1.392 (2)
C3—C4	1.382 (3)	C16—C17	1.397 (2)
C3—H3	0.9300	C17—C18	1.378 (2)
C4—C5	1.372 (2)	C17—H17	0.9300
C4—H4	0.9300	C18—C19	1.380 (3)
C5—C6	1.409 (2)	C18—H18	0.9300
C5—H5	0.9300	C19—C20	1.363 (3)
C7—C16	1.4798 (18)	C19—H19	0.9300
C7—C8	1.5153 (18)	C20—C21	1.391 (2)
C8—C9	1.5048 (18)	C20—H20	0.9300
C8—H8A	0.9700	C21—H21	0.9300
C8—H8B	0.9700

C9—S1—C10	102.08 (7)	C11—C10—H10B	108.8
C9—N1—C1	120.03 (12)	S1—C10—H10B	108.8
C7—N2—C6	121.68 (12)	H10A—C10—H10B	107.7
C11—N3—C12	116.61 (17)	N3—C11—C15	124.42 (16)
C2—C1—C6	118.71 (13)	N3—C11—C10	115.42 (14)
C2—C1—N1	116.01 (13)	C15—C11—C10	120.15 (15)
C6—C1—N1	125.13 (12)	N3—C12—C13	123.8 (2)
C3—C2—C1	121.45 (16)	N3—C12—H12	118.1
C3—C2—H2	119.3	C13—C12—H12	118.1
C1—C2—H2	119.3	C12—C13—C14	118.48 (18)
C2—C3—C4	119.99 (15)	C12—C13—H13	120.8
C2—C3—H3	120.0	C14—C13—H13	120.8
C4—C3—H3	120.0	C13—C14—C15	118.54 (19)
C5—C4—C3	119.71 (16)	C13—C14—H14	120.7
C5—C4—H4	120.1	C15—C14—H14	120.7
C3—C4—H4	120.1	C11—C15—C14	118.06 (18)
C4—C5—C6	121.63 (16)	C11—C15—H15	121.0
C4—C5—H5	119.2	C14—C15—H15	121.0
C6—C5—H5	119.2	C21—C16—C17	118.15 (13)
N2—C6—C1	125.25 (12)	C21—C16—C7	122.20 (13)
N2—C6—C5	116.12 (13)	C17—C16—C7	119.65 (12)
C1—C6—C5	118.29 (13)	C18—C17—C16	121.08 (16)
N2—C7—C16	118.45 (12)	C18—C17—H17	119.5
N2—C7—C8	120.53 (12)	C16—C17—H17	119.5
C16—C7—C8	121.02 (11)	C17—C18—C19	119.72 (17)
C9—C8—C7	106.37 (10)	C17—C18—H18	120.1
C9—C8—H8A	110.5	C19—C18—H18	120.1
C7—C8—H8A	110.5	C20—C19—C18	120.30 (16)
C9—C8—H8B	110.5	C20—C19—H19	119.9
C7—C8—H8B	110.5	C18—C19—H19	119.9
H8A—C8—H8B	108.6	C19—C20—C21	120.55 (17)
N1—C9—C8	124.16 (12)	C19—C20—H20	119.7
N1—C9—S1	122.13 (10)	C21—C20—H20	119.7
C8—C9—S1	113.68 (10)	C20—C21—C16	120.18 (16)
C11—C10—S1	113.92 (10)	C20—C21—H21	119.9
C11—C10—H10A	108.8	C16—C21—H21	119.9
S1—C10—H10A	108.8

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C21—H21···N3ⁱ	0.93	2.56	3.411 (2)	152
C13—H13···N1ⁱⁱ	0.93	2.67	3.554 (2)	160

Symmetry codes: (i) −x+3/2, y−1/2, −z+3/2; (ii) x, y+1, z.

Experimental details

Crystal data
Chemical formula	C₂₁H₁₇N₃S
M_r	343.44
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	296
a, b, c (Å)	14.2995 (3), 8.7004 (2), 14.3851 (4)
β (°)	103.337 (1)
V (Å³)	1741.40 (7)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.19
Crystal size (mm)	0.38 × 0.22 × 0.12

Data collection
Diffractometer	Bruker X8 APEXII KappaCCD area-detector
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	25788, 5841, 4115
R_int	0.027
(sin θ/λ)_max (Å⁻¹)	0.738

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.044, 0.152, 1.11
No. of reflections	5841
No. of parameters	226
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.44, −0.23

Computer programs: APEX2 (Bruker, 2005), APEX2, SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), ORTEP-3 for Windows (Farrugia, 1997), WinGX (Farrugia, 1999).