Crystal structure of 3-benzyl­sulfanyl-6-(5-methyl-1,2-oxazol-3-yl)-1,2,4-triazolo[3,4-b][1,3,4]thia­diazole

Krishnaiah Vaarla; V Rajeswar Rao; Mehmet Akkurt

doi:10.1107/S2056989015017351

. 2015 Oct 3;71(Pt 11):o809–o810. doi: 10.1107/S2056989015017351

Crystal structure of 3-benzylsulfanyl-6-(5-methyl-1,2-oxazol-3-yl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole

Krishnaiah Vaarla ^a, V Rajeswar Rao ^a,^*, Mehmet Akkurt ^b

PMCID: PMC4645033 PMID: 26594538

Abstract

In the title compound, C₁₄H₁₁N₅OS₂, the triazolo–thiadiazole system is essentially planar (r.m.s. deviation = 0.002 Å) and makes dihedral angles of 6.33 (12) and 42.95 (14)° with the planes of the oxazole and phenyl rings, respectively. In the crystal, face-to-face π–π interactions are observed between the thiadiazole and oxazole rings [centroid–centroid distance = 3.4707 (18) Å], leading to columns along [010].

Keywords: crystal structure, triazolo–thiadiazole system, isoxazole ring

Related literature

For the pharmocological properties of isoxazole, see: Kuz’min et al. (2007 ▸); Yermolina et al. (2011 ▸); Lilienkampf et al. (2010 ▸); Kamal et al. (2011 ▸). For the bioactivity of 1,2,4-triazoles coupled with the thiadiazole heterocylic ring system, see: Singh & Singh (2009 ▸). For biological applications, such as antimicrobial, anticancer, antiviral and antihelmentic properties, see: Habib et al. (1997 ▸); Bhat et al. (2004 ▸); Farghaly et al. (2006 ▸); Khalil et al. (1999 ▸). For the synthesis, see: Vaarla & Rao (2014 ▸). For a similar structure, see: Dinçer et al. (2005 ▸).

Experimental

Crystal data

C₁₄H₁₁N₅OS₂
M _r = 329.40
Orthorhombic,
a = 16.271 (5) Å
b = 5.3804 (13) Å
c = 16.700 (4) Å
V = 1462.0 (7) Å³
Z = 4
Mo Kα radiation
μ = 0.37 mm⁻¹
T = 296 K
0.50 × 0.45 × 0.30 mm

Data collection

Bruker Kappa APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 1999 ▸) T _min = 0.836, T _max = 0.896
10433 measured reflections
3117 independent reflections
2905 reflections with I > 2σ(I)
R _int = 0.027

Refinement

R[F ² > 2σ(F ²)] = 0.031
wR(F ²) = 0.077
S = 1.08
3117 reflections
200 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.20 e Å⁻³
Absolute structure: Flack (1983 ▸)
Absolute structure parameter: 0.02 (2)

Data collection: APEX2 (Bruker, 2004 ▸); cell refinement: APEX2 and SAINT (Bruker, 2004 ▸); data reduction: SAINT and XPREP (Bruker, 2004 ▸); program(s) used to solve structure: SIR92 (Altomare et al., 1993 ▸); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015 ▸); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▸); software used to prepare material for publication: WinGX (Farrugia, 2012 ▸) and PLATON (Spek, 2009 ▸).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S2056989015017351/tk5386sup1.cif

e-71-0o809-sup1.cif^{(23KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989015017351/tk5386Isup2.hkl

e-71-0o809-Isup2.hkl^{(171.2KB, hkl)}

Click here for additional data file.^{(5.9KB, cml)}

Supporting information file. DOI: 10.1107/S2056989015017351/tk5386Isup3.cml

Click here for additional data file.^{(1.1MB, tif)}

. DOI: 10.1107/S2056989015017351/tk5386fig1.tif

The title molecule with the atom numbering scheme. Displacement ellipsoids for non-H atoms are drawn at the 30% probability level.

Click here for additional data file.^{(3.9MB, tif)}

b . DOI: 10.1107/S2056989015017351/tk5386fig2.tif

View of the molecular packing of the title compound down the b axis. All H atoms have been omitted for clarity.

CCDC reference: 1425251

Additional supporting information: crystallographic information; 3D view; checkCIF report

Acknowledgments

We are thankful to the Director N.I.T. Warangal for providing research facilities. KV express thanks to University Grants Commission–New Delhi (UGC) for a Senior Research Fellowship. The authors are thankful to SAIF–KOCHI–Cochin University, India, for providing the single crystal X-ray data.

supplementary crystallographic information

S1. Comment

Nitrogen heterocyclic compounds have received much attention among researchers throughout the world for their applications as biological probes in the field of drug discovery. Isoxazole is a five membered O- and N-containing heterocylic compound and widely used as key building pharmacophore for drugs (Kuz'min et al., 2007; Yermolina et al., 2011; Lilienkampf et al., 2010; Kamal et al., 2011). Isoxazoles have a wide range of biological applications such as antiviral, anticancer, antibiotic, antituberculosis, antiinflammatory and antimicrobial agents, and as COX-2 inhibitors (Singh & Singh, 2009).

A large number of [1,2,4] triazolo[3,4-b][1,3,4]thiadiazoles have remarkable biological applications such as antimicrobial (Habib et al., 1997), anticancer (Bhat et al., 2004), antiviral (Farghaly et al., 2006) and antihelmentic (Khalil et al., 1999) properties.

The title molecule is shown in Fig. 1. The plane of the triazolo-thiadiazole system [r.m.s. deviation = 0.002 Å] forms dihedral angles of 6.33 (12) and 42.95 (14)° with the oxazole (O1/N1/C2–C4) and phenyl (C9–C14) rings, respectively. All the bond lengths and bond angles in the compound are within normal ranges and comparable with those reported in a similar compound (Dinçer et al., 2005).

The crystal structure is stabilized by face-to-face π—π interactions [Cg1···Cg2 (x, -1 + y, z) = 3.4707 (18) Å and Cg2···Cg1 (x, 1 + y, z) = 3.4707 (18) Å] between the ring centroids, Cg1 and Cg2, of the thiadiazole and oxazole rings, respectively. Fig. 2 shows the molecular packing of the title compound down the b axis.

S2. Experimental

The title compound was synthesized according to the published procedure (Vaarla & Rao, 2014). The compound was synthesized in two steps. In step one, a mixture containing equivalent amounts of 5-methylisoxazole-3-carboxylic acid and 4-amino-4H-[1,2,4]triazole-3,5-dithiol was refluxed in the presence of phosphorus oxychloride for about 5 h. After monitoring by TLC, the reaction mixture was cooled to room temperature and poured into crushed ice. The separated solid was filtered, dried and recrystallized from methanol.

In the second step the intermediate 6-(5-methylisoxazol-3-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole-3-thiol (1 eq.) was treated with benzyl bromide (1.1 eq.) in ethanol. The reaction mixture was refluxed for 5 h. After completion of the reaction, the reaction mixture was cooled to room temperature. The isolated solid product was filtered and washed with ethanol. Recrystallization was from ethanol.