3,4-Di­hydro-2H-benzo[4,5]imidazo[2,1-b][1,3]thia­zin-3-ol

El Ouasif, L.; El Ghoul, M.; Achour, R.; Saadi, M.; El Ammari, L.

doi:10.1107/S2414314617004291

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 2| Part 3| March 2017| x170429

https://doi.org/10.1107/S2414314617004291

Open

access

3,4-Dihydro-2H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-3-ol

Latifa El Ouasif,^a Mostafa El Ghoul,^a ^* Redouane Achour,^a Mohamed Saadi ^b and Lahcen El Ammari ^b

^aLaboratoire de Chimie Organique Hétérocyclique URAC 21, Pôle de Compétences Pharmacochimie, Mohammed V University in Rabat, BP 1014 Avenue Ibn Batouta, Rabat, Morocco, and ^bLaboratoire de Chimie du Solide Appliquée, Faculty of Sciences, Mohammed V University in Rabat, Avenue Ibn Batouta, BP 1014, Rabat, Morocco
^*Correspondence e-mail: elghoulmostafa00@gmail.com

Edited by H. Stoeckli-Evans, University of Neuchâtel, Switzerland (Received 15 March 2017; accepted 17 March 2017; online 24 March 2017)

In the title compound, C₁₀H₁₀N₂OS, the benzimidazole ring system is almost planar (r.m.s. deviation = 0.007 Å), whereas the heterocyclic six-membered thiazine ring has an envelope conformation, with the hydroxy-substituted C atom as the flap. In the crystal, molecules are linked by O—H⋯N hydrogen bonds to form zigzag chains running along the b-axis direction. The chains are linked by C—H⋯O hydrogen bonds and C—H⋯π interactions, forming layers parallel to the bc plane.

Keywords: crystal structure; benzimidazole; heterocyclic system; 2-mercaptobenzimidazoles; thiazine; hydrogen bonding; C—H⋯π interactions.

CCDC reference: 1538649

Structure description

The benzimidazole heterocyclic system is an important pharmacophore and privileged structure in the medicinal chemistry. Its derivatives, and particularly 2-mercaptobenzimidazoles, exert various biological activities such as anticonvulsant (Anandarajagopal et al., 2010 ; Bansal & Silakari, 2012 ), antiviral, anticancer (Enumula et al., 2014 ), anti-ulcer (Gaba et al., 2014 ), antioxidant, antibacterial (Mavrova et al., 2015 ), antiprotozoal (Pérez-Villanueva et al., 2013 ; Walia et al., 2013 ) and antimicrobial (Yaseen et al., 2010 ). The 2-mercaptobenzimidazole ring system is present in the structures of many antiparasitic, anthelmintic, antifungal, antiviral and antitumor drugs. In the present work, we have studied the action of epichlorhydrin towards 2-mercaptobenzimidazole in 2-propanol in the presence of a saturated aqueous solution of sodium bicarbonate. This led to the characterized title compound.

The molecular structure of the title compound is shown in Fig. 1. The benzimidazole ring system (N1/N2/C1–C7) is almost planar with an r.m.s. deviation of 0.007 Å. The heterocyclic six-membered thiazine ring (S1/N2/C7–C10) has an envelope conformation [puckering parameters: amplitude (Q) = 0.5154 (13) Å, θ = 126.91 (13)°, φ = 63.60 (16)°], with the hydroxy-substituted C atom, C9, as the flap. It deviates from the mean plane through the other 12 atoms of the three-fused ring system by 0.737 (1) Å.

Figure 1
The molecular structure of the title compound, with the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

In the crystal, structural cohesion is ensured by O1—H1⋯N1ⁱ hydrogen bonds, which link the molecules into zigzag chains propagating along the b-axis direction. The chains are linked by C8—H8A⋯O1ⁱⁱ hydrogen bonds to form layers parallel to the bc plane (Fig. 2 and Table 1). Within the layers there are also C—H⋯π interactions present (Table 1 and Fig. 2)

Table 1
Hydrogen-bond geometry (Å, °)

Cg1 is the centroid of the N1/N2/C1/C6/C7 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯N1ⁱ	0.82	2.02	2.7536 (14)	148
C8—H8A⋯O1ⁱⁱ	0.97	2.38	3.2231 (15)	145
C10—H10A⋯Cg1ⁱⁱ	0.97	2.62	3.422 (14)	138
Symmetry codes: (i) x, y+1, z; (ii) $[x, -y+{\script{3\over 2}}, z-{\script{1\over 2}}]$ .

Figure 2
Crystal packing of the title compound, viewed along the a axis, showing molecules linked by hydrogen bonds (dashed lines) and C—H⋯π interactions (blue arrows); see Table 1

for details. For clarity, only H atoms (grey balls) H1, H8A and H10A have been included.

Synthesis and crystallization

A mixture of 2-mercaptobenzimidazole (1 g, 7 mmol) and epichlorhydrin (0.43 g, 4.7 mmol) in 20 ml of a saturated aqueous solution of sodium bicarbonate and 20 ml of 2-propanol, was heated under reflux for 6 h. After cooling, the product which precipitated was filtered, washed with water and then recrystallized from ethanol solution to afford the title compound as colourless block-like crystals (yield 44%; m.p. 485–487 K).

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₀H₁₀N₂OS
M_r	206.26
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	296
a, b, c (Å)	17.570 (3), 6.3994 (10), 8.8690 (15)
β (°)	95.641 (8)
V (Å³)	992.4 (3)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.29
Crystal size (mm)	0.32 × 0.26 × 0.21

Data collection
Diffractometer	Bruker X8 APEX
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 )
T_min, T_max	0.680, 0.747
No. of measured, independent and observed [I > 2σ(I)] reflections	32163, 3459, 2928
R_int	0.027
(sin θ/λ)_max (Å⁻¹)	0.746

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.044, 0.126, 1.08
No. of reflections	3459
No. of parameters	127
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.38, −0.18
Computer programs: APEX2 and SAINT (Bruker, 2009 ), SHELXT2014 (Sheldrick, 2015a ), ORTEP-3 for Windows (Farrugia, 2012 ), Mercury (Macrae et al., 2008 ), SHELXL2014 (Sheldrick, 2015b ) and publCIF (Westrip, 2010 ).

Structural data

CCDC reference: 1538649

Crystal structure: contains datablocks I, block. DOI: https://doi.org/10.1107/S2414314617004291/su4141sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314617004291/su4141Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314617004291/su4141Isup3.cml

checkCIF report

Computing details top

Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXT2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) and Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015b) and publCIF (Westrip, 2010).

3,4-Dihydro-2H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-3-ol top

Crystal data top

C₁₀H₁₀N₂OS	D_x = 1.381 Mg m⁻³
M_r = 206.26	Melting point: 486 K
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
a = 17.570 (3) Å	Cell parameters from 3459 reflections
b = 6.3994 (10) Å	θ = 3.4–32.0°
c = 8.8690 (15) Å	µ = 0.29 mm⁻¹
β = 95.641 (8)°	T = 296 K
V = 992.4 (3) Å³	Block, colourless
Z = 4	0.32 × 0.26 × 0.21 mm
F(000) = 432

Data collection top

Bruker X8 APEX diffractometer	3459 independent reflections
Radiation source: fine-focus sealed tube	2928 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.027
φ and ω scans	θ_max = 32.0°, θ_min = 3.4°
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	h = −26→26
T_min = 0.680, T_max = 0.747	k = −9→9
32163 measured reflections	l = −10→13

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) = 0.126	H-atom parameters constrained
S = 1.08	w = 1/[σ²(F_o²) + (0.0661P)² + 0.1833P] where P = (F_o² + 2F_c²)/3
3459 reflections	(Δ/σ)_max = 0.001
127 parameters	Δρ_max = 0.38 e Å⁻³
0 restraints	Δρ_min = −0.18 e Å⁻³

Special details top

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 (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.79752 (7)	0.5625 (2)	0.73771 (14)	0.0431 (3)
C2	0.87063 (9)	0.6448 (3)	0.7334 (2)	0.0649 (4)
H2	0.8791	0.7703	0.6848	0.078*
C3	0.93005 (11)	0.5291 (5)	0.8056 (3)	0.0882 (7)
H3	0.9798	0.5781	0.8050	0.106*
C4	0.91779 (13)	0.3425 (5)	0.8789 (3)	0.0896 (7)
H4	0.9594	0.2706	0.9264	0.108*
C5	0.84527 (11)	0.2607 (3)	0.8830 (2)	0.0702 (5)
H5	0.8374	0.1357	0.9327	0.084*
C6	0.78427 (8)	0.3732 (2)	0.80974 (15)	0.0456 (3)
C7	0.67468 (7)	0.49009 (16)	0.71854 (12)	0.0353 (2)
C8	0.56819 (8)	0.7590 (2)	0.57928 (13)	0.0430 (3)
H8A	0.5687	0.7336	0.4716	0.052*
H8B	0.5192	0.8212	0.5948	0.052*
C9	0.63086 (8)	0.91282 (18)	0.62946 (12)	0.0396 (2)
H9	0.6212	1.0424	0.5718	0.048*
C10	0.70875 (8)	0.82999 (19)	0.59837 (13)	0.0415 (3)
H10A	0.7094	0.8063	0.4905	0.050*
H10B	0.7476	0.9332	0.6294	0.050*
N1	0.70658 (7)	0.33100 (15)	0.79621 (12)	0.0437 (2)
N2	0.72630 (6)	0.63499 (15)	0.67993 (11)	0.0360 (2)
O1	0.62792 (7)	0.95827 (14)	0.78494 (9)	0.0477 (2)
H1	0.6619	1.0415	0.8129	0.071*
S1	0.57672 (2)	0.51091 (5)	0.67849 (4)	0.04656 (12)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0444 (6)	0.0453 (6)	0.0404 (6)	−0.0054 (5)	0.0084 (5)	−0.0050 (5)
C2	0.0463 (7)	0.0770 (11)	0.0726 (10)	−0.0131 (7)	0.0112 (7)	−0.0040 (9)
C3	0.0460 (9)	0.120 (2)	0.0986 (17)	−0.0010 (10)	0.0054 (10)	−0.0048 (14)
C4	0.0630 (11)	0.1130 (19)	0.0899 (15)	0.0269 (12)	−0.0080 (10)	−0.0015 (14)
C5	0.0777 (11)	0.0656 (10)	0.0657 (10)	0.0219 (9)	−0.0009 (8)	0.0036 (8)
C6	0.0559 (7)	0.0396 (6)	0.0414 (6)	0.0029 (5)	0.0054 (5)	−0.0042 (5)
C7	0.0461 (6)	0.0282 (4)	0.0321 (5)	−0.0113 (4)	0.0070 (4)	−0.0048 (3)
C8	0.0490 (6)	0.0455 (6)	0.0342 (5)	0.0025 (5)	0.0023 (5)	−0.0068 (4)
C9	0.0614 (7)	0.0310 (5)	0.0274 (4)	−0.0030 (5)	0.0091 (4)	0.0008 (4)
C10	0.0547 (7)	0.0354 (5)	0.0359 (5)	−0.0100 (5)	0.0116 (5)	0.0064 (4)
N1	0.0601 (6)	0.0284 (4)	0.0428 (5)	−0.0071 (4)	0.0065 (4)	−0.0005 (4)
N2	0.0423 (5)	0.0311 (4)	0.0351 (4)	−0.0094 (3)	0.0074 (4)	0.0003 (3)
O1	0.0801 (7)	0.0337 (4)	0.0312 (4)	−0.0166 (4)	0.0157 (4)	−0.0064 (3)
S1	0.04469 (19)	0.04324 (18)	0.0517 (2)	−0.01646 (12)	0.00467 (13)	−0.00391 (12)

Geometric parameters (Å, º) top

C1—N2	1.3847 (17)	C7—N2	1.3641 (13)
C1—C2	1.393 (2)	C7—S1	1.7280 (13)
C1—C6	1.3992 (19)	C8—C9	1.5108 (18)
C2—C3	1.385 (3)	C8—S1	1.8145 (14)
C2—H2	0.9300	C8—H8A	0.9700
C3—C4	1.386 (4)	C8—H8B	0.9700
C3—H3	0.9300	C9—O1	1.4152 (13)
C4—C5	1.381 (3)	C9—C10	1.5179 (19)
C4—H4	0.9300	C9—H9	0.9800
C5—C6	1.397 (2)	C10—N2	1.4601 (15)
C5—H5	0.9300	C10—H10A	0.9700
C6—N1	1.3852 (18)	C10—H10B	0.9700
C7—N1	1.3225 (15)	O1—H1	0.8200

N2—C1—C2	131.71 (14)	S1—C8—H8A	108.8
N2—C1—C6	105.92 (11)	C9—C8—H8B	108.8
C2—C1—C6	122.37 (15)	S1—C8—H8B	108.8
C3—C2—C1	116.11 (19)	H8A—C8—H8B	107.7
C3—C2—H2	121.9	O1—C9—C8	109.00 (10)
C1—C2—H2	121.9	O1—C9—C10	111.64 (11)
C2—C3—C4	122.2 (2)	C8—C9—C10	111.29 (10)
C2—C3—H3	118.9	O1—C9—H9	108.3
C4—C3—H3	118.9	C8—C9—H9	108.3
C5—C4—C3	121.69 (19)	C10—C9—H9	108.3
C5—C4—H4	119.2	N2—C10—C9	111.02 (9)
C3—C4—H4	119.2	N2—C10—H10A	109.4
C4—C5—C6	117.34 (19)	C9—C10—H10A	109.4
C4—C5—H5	121.3	N2—C10—H10B	109.4
C6—C5—H5	121.3	C9—C10—H10B	109.4
N1—C6—C5	130.08 (15)	H10A—C10—H10B	108.0
N1—C6—C1	109.63 (11)	C7—N1—C6	104.98 (10)
C5—C6—C1	120.27 (15)	C7—N2—C1	106.15 (10)
N1—C7—N2	113.32 (11)	C7—N2—C10	126.31 (11)
N1—C7—S1	121.93 (9)	C1—N2—C10	127.51 (10)
N2—C7—S1	124.71 (9)	C9—O1—H1	109.5
C9—C8—S1	113.84 (9)	C7—S1—C8	101.55 (6)
C9—C8—H8A	108.8

Hydrogen-bond geometry (Å, º) top

Cg1 is the centroid of the N1/N2/C1/C6/C7 ring.

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···N1ⁱ	0.82	2.02	2.7536 (14)	148
C8—H8A···O1ⁱⁱ	0.97	2.38	3.2231 (15)	145
C10—H10A···Cg1ⁱⁱ	0.97	2.62	3.422 (14)	138

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

Acknowledgements

The authors thank the Unit of Support for Technical and Scientific Research (UATRS, CNRST) for the X-ray measurements.

References

Anandarajagopal, K., Tiwari, R. N., Bothara, K. G., Anbu Jeba Sunilson, J., Dineshkumar, C. & Promwichit, P. (2010). Adv. Appl. Sci. Res. 1, 132–138. CAS Google Scholar
Bansal, Y. & Silakari, O. (2012). Bioorg. Med. Chem. 20, 6208–6236. Web of Science CrossRef CAS PubMed Google Scholar
Bruker (2009). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Enumula, S., Pangal, A., Gazge, M., Shaikh, J. A. & Ahmed, K. (2014). Res. J. Chem. Sci. 4, 78–88. CAS Google Scholar
Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854. Web of Science CrossRef CAS IUCr Journals Google Scholar
Gaba, M., Singh, S. & Mohan, C. (2014). Eur. J. Med. Chem. 76, 494–505. CrossRef CAS PubMed Google Scholar
Krause, L., Herbst-Irmer, R., Sheldrick, G. M. & Stalke, D. (2015). J. Appl. Cryst. 48, 3–10. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466–470. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Mavrova, A. Ts., Yancheva, D., Anastassova, N., Anichina, K., Zvezdanovic, J., Djordjevic, A., Markovic, D. & Smelcerovic, A. (2015). Bioorg. Med. Chem. 23, 6317–6326. CrossRef CAS PubMed Google Scholar
Pérez-Villanueva, J., Hernández-Campos, A., Yépez-Mulia, L., Méndez-Cuesta, C., Méndez-Lucio, O., Hernández-Luis, F. & Castillo, R. (2013). Bioorg. Med. Chem. Lett. 23, 4221–4224. PubMed Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Walia, R., Hedaitullah, Md., Naaz, S. F., Iqbal, K. & Lamba, H. S. (2013). Int. J. Res. Pharm. Chem. 1, 565–574. Google Scholar
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925. Web of Science CrossRef CAS IUCr Journals Google Scholar
Yaseen, G. & Sudhakar, J. (2010). Int. J. Pharm. Bio Sci. 1, 281–286. Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

IUCrDATA

ISSN: 2414-3146

Volume 2| Part 3| March 2017| x170429

https://doi.org/10.1107/S2414314617004291

Open

access

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Plain Text
		Text

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Plain Text
		Text

Search IUCr Journals		doi		Advanced search
Author		volume	page

organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

3,4-Di­hydro-2H-benzo[4,5]imidazo[2,1-b][1,3]thia­zin-3-ol

Structure description

Synthesis and crystallization

Refinement

Structural data

Acknowledgements

References

organic compounds

3,4-Dihydro-2H-benzo[4,5]imidazo[2,1-b][1,3]thiazin-3-ol