5-Chloro-N-(4,5-dihydro-1H-imidazol-2-yl)-2,1,3-benzothia­diazol-4-amine (tizanidine)

Peter John; Islam Ullah Khan; Mehmet Akkurt; Muhammad Shahid Ramzan; Shahzad Sharif

doi:10.1107/S1600536811008348

. 2011 Mar 12;67(Pt 4):o838–o839. doi: 10.1107/S1600536811008348

5-Chloro-N-(4,5-dihydro-1H-imidazol-2-yl)-2,1,3-benzothiadiazol-4-amine (tizanidine)

Peter John ^a, Islam Ullah Khan ^a, Mehmet Akkurt ^b,^*, Muhammad Shahid Ramzan ^a, Shahzad Sharif ^a

PMCID: PMC3100067 PMID: 21754121

Abstract

There are two independent molecules (A and B) with similar conformations in the asymmetric unit of the title compound, C₉H₈ClN₅S. The benzothiadiazole ring systems of both molecules are essentially planar [maximum deviation = 0.021 (2) Å in molecule A and 0.022 (1) Å in molecule B] and make dihedral angles of 68.78 (9) and 54.39 (8)°, respectively, with the mean planes of their 4,5-dihydro-1H-imidazole rings. An intramolecular N—H⋯Cl hydrogen bond occurs in molecule B. In the crystal, both molecules form centrosymmetric dimers through π-stacking of their benzothiadiazole rings, with interplanar distances of 3.3174 (7) and 3.2943 (6) Å. These dimers are further linked via pairs of N—H⋯N hydrogen bonds with the dihydroimidazole rings as the hydrogen-bonding donors and one of the benzothiadiazole N atoms as the acceptors, generating R ₂ ²(16) ring motifs. The A ₂ and B ₂ dimers in turn form additional N—H⋯N hydrogen bonds with the secondary amine as the H-atom donor and the dihydroimidazole N atom as the acceptor. These R ₂ ²(8)-type interactions connect the A ₂ and B ₂ dimers with each other, forming infinite chains along [1 Inline graphic 1].

Related literature

For the medicinal importance of tizanidine, see: Koch et al. (1989 ▶); Shellenberger et al. (1999 ▶); Tse et al. (1987 ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶).

Experimental

Crystal data

C₉H₈ClN₅S
M _r = 253.72
Triclinic,
a = 7.6927 (3) Å
b = 10.8558 (4) Å
c = 12.9969 (5) Å
α = 95.790 (1)°
β = 101.126 (1)°
γ = 92.192 (1)°
V = 1057.69 (7) Å³
Z = 4
Mo Kα radiation
μ = 0.54 mm⁻¹
T = 296 K
0.29 × 0.18 × 0.08 mm

Data collection

Bruker APEXII CCD diffractometer
17897 measured reflections
5104 independent reflections
4449 reflections with I > 2σ(I)
R _int = 0.024

Refinement

R[F ² > 2σ(F ²)] = 0.042
wR(F ²) = 0.120
S = 1.03
5104 reflections
302 parameters
5 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.65 e Å⁻³
Δρ_min = −0.43 e Å⁻³

Data collection: APEX2 (Bruker, 2007 ▶); cell refinement: SAINT (Bruker, 2007 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶) and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811008348/zl2351sup1.cif

e-67-0o838-sup1.cif^{(23.8KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811008348/zl2351Isup2.hkl

e-67-0o838-Isup2.hkl^{(249.9KB, hkl)}

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
N3A—HN3A⋯N5B	0.92 (2)	2.10 (2)	3.003 (2)	168 (3)
N4A—HN4A⋯N1Aⁱ	0.86 (3)	2.38 (3)	3.205 (3)	160 (2)
N3B—HN3B⋯N5A	0.88 (2)	1.98 (2)	2.864 (2)	177 (2)
N4B—HN4B⋯Cl1B	0.84 (2)	2.75 (2)	3.1927 (15)	114 (2)
N4B—HN4B⋯N1Bⁱⁱ	0.84 (2)	2.48 (2)	3.227 (2)	150 (2)

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

The authors are grateful to the Higher Education Commission (HEC), Pakistan, for providing funds for the single-crystal XRD facilities at GC University, Lahore.

supplementary crystallographic information

Comment

Tizanidine {or (5-chloro-N-(4,5-dihydro-1H-imidazol-2-yl)-2,1,3-benzothiadiazol-4-amine)} is an adrenergic agonist and proved to be an active myotonolytic skeletal muscle relaxant with a chemical structure different from other muscle relaxants (Koch et al., 1989; Tse et al., 1987). It also reduces increased muscle tone associated with spasticity in patients with multiple sclerosis or spinal cord injury (Shellenberger et al., 1999). Herein, we report the crystal structure of Tizanidine.

The title compound crystallized with two unique molecules A and B in the asymmetric unit (Fig. 1). The benzothiadiazole ring systems (S1A/N1A/N2A/C1A–C6A and S1B/N1B/N2B/C1B) of both molecules A and B are essentially planar [max. deviations = 0.021 (2) Å for C5A in molecule A and 0.022 (1) Å for C6B in molecule B] and they form dihedral angles of 68.78 (9) and 54.39 (8)°, respectively, with the mean planes of their 4,5-dihydro-1H-imidazole rings (N4A/N5A/C7A–C9A and N4B/N5B/C7B–C9B). The conformations of molecules A and B are similar (Fig. 2).

Molecular conformations in the crystal structure are stabilized by intramolecular N—H···N and N—H···Cl interactions (Table 1). Both molecules A and B are forming centrosymmetric dimers through π-stacking of their benzothiadiazole rings with interplanar distances of 3.3174 (7) and 3.2943 (6) Å [Cg1···Cg2ⁱⁱ = 3.6026 (10) Å and Cg3···Cg4^iv = 3.5096 (9) Å; symmetry codes: (i) 1-x, 1-y, 1-z; (ii) 3-x, -y, 2-z; Cg1, Cg2, Cg3 and Cg4 are the centroids of the S1A/N1A/N2A/C4A/C5A, C1A–C6A, S1B/N1B/N2B/C4B/C5B and C1B–C6B rings, respectively]. These dimers are further tied together via pairs of N—H···N hydrogen-bonds with the dihydroimidazole rings as the hydrogen bonding donor (Table 1 and Fig. 3) and one of the benzothiadiazole N atoms as the acceptor, generating rings of graph set motifs of the type R²₂(16) (Bernstein et al., 1995). The A₂ and B₂ dimers do in turn form additional N—H···N hydrogen-bonds, with the secondary amine as the H donor and the dihydroimidazole N atom as the acceptor. These R²₂(8) type interactions connect the A₂ and B₂ dimers with each other to form infinite chains that stretch along the (1 -1 1) direction of the unit cell (Fig. 3).

Experimental

To 0.3 g of tizanidine in 10 ml methanol were added several drops of sodium hydroxide solution (3%) to adjust the pH to 8. The resulting solution was left for slow evaporation. Orange crystals were obtained after three days.