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

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].

Key indicators

• Single-crystal X-ray study
• T = 296 K
• Mean [sigma](C-C) = 0.004 Å
• R factor = 0.031
• wR factor = 0.077
• Data-to-parameter ratio = 15.6

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT340_ALERT_3_C Low Bond Precision on  C-C Bonds ...............     0.0043 Ang.
PLAT915_ALERT_3_C Low Friedel Pair Coverage ......................         72 %

Alert level G
PLAT066_ALERT_1_G Predicted and Reported Tmin&Tmax Range Identical          ? Check
PLAT910_ALERT_3_G Missing # of FCF Reflection(s) Below Th(Min) ...          2 Report
PLAT912_ALERT_4_G Missing # of FCF Reflections Above STh/L=  0.600         42 Note

   0 ALERT level A = Most likely a serious problem - resolve or explain
   0 ALERT level B = A potentially serious problem, consider carefully
   2 ALERT level C = Check. Ensure it is not caused by an omission or oversight
   3 ALERT level G = General information/check it is not something unexpected

   1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   3 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

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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.

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).

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.

S3. Refinement

All H atoms were placed in calculated positions with C—H = 0.93 to 0.97 Å, refined in the riding model with U_iso(H) parameters set to 1.2U_eq(C) or 1.5U_eq (CH₃ only). The (0 0 - 2), (2 0 1) and (2 0 0) reflections, whose intensities were affected by the beamstop, were removed from the final refinement.

Computing details

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).

Figures

	Fig. 1. The title molecule with the atom numbering scheme. Displacement ellipsoids for non-H atoms are drawn at the 30% probability level.
	Fig. 2. View of the molecular packing of the title compound down the b axis. All H atoms have been omitted for clarity.

3-Benzylsulfanyl-6-(5-methyl-1,2-oxazol-3-yl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole

Crystal data

C14H11N5OS2	F(000) = 680
Mr = 329.40	Dx = 1.497 Mg m^−3
Orthorhombic, Pca21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2c -2ac	Cell parameters from 5610 reflections
a = 16.271 (5) Å	θ = 5.0–55.6°
b = 5.3804 (13) Å	µ = 0.37 mm^−1
c = 16.700 (4) Å	T = 296 K
V = 1462.0 (7) Å^3	Block, colourless
Z = 4	0.50 × 0.45 × 0.30 mm

Data collection

Bruker Kappa APEXII CCD diffractometer	3117 independent reflections
Radiation source: fine-focus sealed tube	2905 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.027
ω and φ scan	θmax = 28.4°, θmin = 2.8°
Absorption correction: multi-scan (SADABS; Bruker, 1999)	h = −20→21
Tmin = 0.836, Tmax = 0.896	k = −6→7
10433 measured reflections	l = −16→21

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.031	w = 1/[σ^2(Fo^2) + (0.0411P)^2 + 0.1925P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.077	(Δ/σ)max = 0.001
S = 1.08	Δρmax = 0.18 e Å^−3
3117 reflections	Δρmin = −0.20 e Å^−3
200 parameters	Absolute structure: Flack (1983)
1 restraint	Absolute structure parameter: 0.02 (2)

Special details

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement on F² for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The observed criterion of F² > σ(F²) is used only for calculating -R-factor-obs 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
S1	0.58876 (4)	0.55792 (12)	0.27749 (5)	0.0430 (2)
S2	0.56435 (4)	0.13539 (13)	0.56223 (5)	0.0480 (2)
O1	0.41434 (13)	1.1668 (4)	0.26095 (13)	0.0513 (7)
N1	0.47539 (15)	0.9833 (5)	0.26294 (16)	0.0500 (9)
N2	0.51832 (12)	0.5539 (4)	0.41898 (14)	0.0359 (6)
N3	0.57592 (12)	0.3670 (4)	0.41555 (14)	0.0348 (6)
N4	0.66919 (15)	0.1462 (4)	0.35159 (18)	0.0478 (8)
N5	0.65754 (15)	0.0517 (4)	0.42870 (17)	0.0464 (8)
C1	0.30250 (19)	1.3389 (5)	0.3361 (2)	0.0539 (10)
C2	0.37083 (16)	1.1579 (4)	0.32957 (17)	0.0396 (8)
C3	0.40056 (18)	0.9771 (5)	0.37679 (18)	0.0415 (8)
C4	0.46538 (15)	0.8755 (4)	0.33223 (17)	0.0350 (7)
C5	0.52042 (14)	0.6671 (4)	0.35064 (17)	0.0342 (7)
C6	0.61891 (16)	0.3354 (4)	0.34707 (18)	0.0381 (7)
C7	0.60185 (15)	0.1833 (5)	0.46600 (18)	0.0388 (8)
C8	0.61793 (19)	0.3882 (5)	0.6143 (2)	0.0488 (9)
C9	0.70934 (17)	0.3711 (4)	0.60716 (16)	0.0391 (8)
C10	0.7528 (2)	0.5388 (5)	0.5610 (2)	0.0523 (9)
C11	0.8368 (2)	0.5174 (7)	0.5528 (3)	0.0639 (11)
C12	0.8789 (2)	0.3276 (7)	0.5891 (2)	0.0603 (11)
C13	0.8372 (2)	0.1623 (6)	0.6353 (3)	0.0628 (11)
C14	0.7532 (2)	0.1828 (6)	0.6448 (2)	0.0556 (11)
H1A	0.32400	1.49870	0.35070	0.0810*
H1B	0.26440	1.28400	0.37630	0.0810*
H1C	0.27480	1.35110	0.28550	0.0810*
H3	0.38240	0.93020	0.42740	0.0500*
H8A	0.59980	0.54590	0.59240	0.0590*
H8B	0.60300	0.38470	0.67050	0.0590*
H10	0.72510	0.66720	0.53530	0.0630*
H11	0.86540	0.63330	0.52220	0.0770*
H12	0.93530	0.31210	0.58220	0.0730*
H13	0.86540	0.03440	0.66070	0.0750*
H14	0.72560	0.06900	0.67690	0.0670*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0443 (3)	0.0412 (3)	0.0434 (4)	0.0021 (3)	0.0010 (3)	−0.0021 (3)
S2	0.0399 (3)	0.0460 (3)	0.0582 (4)	−0.0038 (3)	0.0005 (4)	0.0125 (3)
O1	0.0461 (11)	0.0513 (11)	0.0566 (15)	0.0077 (8)	−0.0012 (9)	0.0149 (10)
N1	0.0457 (13)	0.0496 (13)	0.0546 (18)	0.0096 (10)	0.0017 (11)	0.0107 (12)
N2	0.0286 (10)	0.0314 (10)	0.0476 (13)	0.0009 (7)	−0.0017 (9)	−0.0029 (9)
N3	0.0276 (9)	0.0299 (10)	0.0470 (13)	0.0001 (7)	−0.0024 (9)	−0.0055 (9)
N4	0.0436 (13)	0.0434 (12)	0.0564 (15)	0.0092 (10)	−0.0002 (12)	−0.0080 (11)
N5	0.0415 (12)	0.0367 (12)	0.0611 (16)	0.0062 (9)	−0.0050 (12)	−0.0029 (11)
C1	0.0434 (15)	0.0392 (14)	0.079 (2)	0.0064 (11)	−0.0022 (16)	0.0071 (15)
C2	0.0334 (12)	0.0312 (12)	0.0543 (17)	−0.0041 (9)	−0.0055 (11)	−0.0018 (12)
C3	0.0426 (14)	0.0345 (12)	0.0474 (17)	0.0023 (10)	−0.0002 (12)	0.0018 (12)
C4	0.0322 (11)	0.0280 (10)	0.0449 (15)	−0.0040 (8)	−0.0077 (10)	−0.0004 (10)
C5	0.0303 (11)	0.0272 (11)	0.0450 (15)	−0.0033 (8)	−0.0048 (11)	−0.0058 (10)
C6	0.0332 (12)	0.0334 (11)	0.0478 (15)	−0.0024 (9)	−0.0036 (12)	−0.0068 (11)
C7	0.0312 (12)	0.0342 (12)	0.0509 (16)	−0.0024 (9)	−0.0054 (11)	−0.0011 (11)
C8	0.0520 (17)	0.0423 (14)	0.0522 (18)	0.0040 (12)	0.0088 (14)	−0.0035 (13)
C9	0.0451 (14)	0.0368 (12)	0.0354 (14)	−0.0027 (10)	0.0008 (11)	−0.0051 (11)
C10	0.0605 (17)	0.0420 (14)	0.0544 (17)	−0.0026 (12)	−0.0032 (17)	0.0069 (14)
C11	0.059 (2)	0.0688 (19)	0.064 (2)	−0.0199 (16)	0.0027 (18)	0.0050 (18)
C12	0.0470 (17)	0.072 (2)	0.062 (2)	−0.0033 (15)	−0.0081 (15)	−0.0165 (18)
C13	0.057 (2)	0.0575 (19)	0.074 (2)	0.0046 (15)	−0.0232 (18)	0.0005 (17)
C14	0.0602 (19)	0.0467 (16)	0.060 (2)	−0.0040 (13)	−0.0082 (15)	0.0126 (15)

Geometric parameters (Å, º)

S1—C5	1.753 (3)	C8—C9	1.495 (4)
S1—C6	1.739 (3)	C9—C10	1.382 (4)
S2—C7	1.738 (3)	C9—C14	1.390 (4)
S2—C8	1.835 (3)	C10—C11	1.378 (5)
O1—N1	1.401 (3)	C11—C12	1.371 (5)
O1—C2	1.348 (4)	C12—C13	1.359 (5)
N1—C4	1.305 (4)	C13—C14	1.380 (5)
N2—N3	1.376 (3)	C1—H1A	0.9600
N2—C5	1.294 (4)	C1—H1B	0.9600
N3—C6	1.351 (4)	C1—H1C	0.9600
N3—C7	1.366 (4)	C3—H3	0.9300
N4—N5	1.397 (4)	C8—H8A	0.9700
N4—C6	1.308 (3)	C8—H8B	0.9700
N5—C7	1.308 (4)	C10—H10	0.9300
C1—C2	1.482 (4)	C11—H11	0.9300
C2—C3	1.342 (4)	C12—H12	0.9300
C3—C4	1.402 (4)	C13—H13	0.9300
C4—C5	1.468 (3)	C14—H14	0.9300
C5—S1—C6	86.79 (13)	C10—C9—C14	117.8 (3)
C7—S2—C8	99.29 (14)	C9—C10—C11	120.6 (3)
N1—O1—C2	109.1 (2)	C10—C11—C12	120.9 (3)
O1—N1—C4	104.2 (2)	C11—C12—C13	119.3 (3)
N3—N2—C5	106.8 (2)	C12—C13—C14	120.5 (3)
N2—N3—C6	118.7 (2)	C9—C14—C13	121.0 (3)
N2—N3—C7	135.6 (2)	C2—C1—H1A	110.00
C6—N3—C7	105.7 (2)	C2—C1—H1B	109.00
N5—N4—C6	104.6 (2)	C2—C1—H1C	109.00
N4—N5—C7	109.6 (2)	H1A—C1—H1B	109.00
O1—C2—C1	115.7 (2)	H1A—C1—H1C	109.00
O1—C2—C3	109.6 (2)	H1B—C1—H1C	109.00
C1—C2—C3	134.7 (3)	C2—C3—H3	128.00
C2—C3—C4	104.0 (3)	C4—C3—H3	128.00
N1—C4—C3	113.0 (2)	S2—C8—H8A	109.00
N1—C4—C5	116.7 (2)	S2—C8—H8B	109.00
C3—C4—C5	130.2 (3)	C9—C8—H8A	109.00
S1—C5—N2	118.27 (17)	C9—C8—H8B	109.00
S1—C5—C4	119.8 (2)	H8A—C8—H8B	108.00
N2—C5—C4	121.9 (2)	C9—C10—H10	120.00
S1—C6—N3	109.44 (17)	C11—C10—H10	120.00
S1—C6—N4	138.7 (2)	C10—C11—H11	120.00
N3—C6—N4	111.9 (3)	C12—C11—H11	119.00
S2—C7—N3	124.7 (2)	C11—C12—H12	120.00
S2—C7—N5	127.1 (2)	C13—C12—H12	120.00
N3—C7—N5	108.2 (3)	C12—C13—H13	120.00
S2—C8—C9	112.91 (19)	C14—C13—H13	120.00
C8—C9—C10	120.9 (2)	C9—C14—H14	120.00
C8—C9—C14	121.3 (2)	C13—C14—H14	119.00
C5—S1—C6—N4	178.0 (3)	N5—N4—C6—N3	−0.3 (3)
C6—S1—C5—N2	−0.6 (2)	N5—N4—C6—S1	−178.5 (2)
C6—S1—C5—C4	−178.2 (2)	C6—N4—N5—C7	0.5 (3)
C5—S1—C6—N3	−0.21 (18)	N4—N5—C7—N3	−0.4 (3)
C8—S2—C7—N5	104.8 (3)	N4—N5—C7—S2	178.5 (2)
C8—S2—C7—N3	−76.5 (2)	C1—C2—C3—C4	178.8 (3)
C7—S2—C8—C9	−58.4 (2)	O1—C2—C3—C4	−0.1 (3)
N1—O1—C2—C1	−179.0 (2)	C2—C3—C4—C5	−178.1 (3)
C2—O1—N1—C4	−0.2 (3)	C2—C3—C4—N1	−0.1 (3)
N1—O1—C2—C3	0.1 (3)	C3—C4—C5—N2	−5.1 (4)
O1—N1—C4—C3	0.1 (3)	N1—C4—C5—S1	−5.5 (3)
O1—N1—C4—C5	178.5 (2)	N1—C4—C5—N2	176.9 (2)
C5—N2—N3—C6	−1.3 (3)	C3—C4—C5—S1	172.5 (2)
N3—N2—C5—C4	178.7 (2)	S2—C8—C9—C10	109.4 (3)
N3—N2—C5—S1	1.1 (3)	S2—C8—C9—C14	−68.8 (3)
C5—N2—N3—C7	−178.4 (3)	C8—C9—C10—C11	−178.1 (3)
N2—N3—C7—S2	−1.4 (4)	C14—C9—C10—C11	0.2 (5)
N2—N3—C6—N4	−177.8 (2)	C8—C9—C14—C13	177.4 (3)
C6—N3—C7—N5	0.2 (3)	C10—C9—C14—C13	−1.0 (5)
C7—N3—C6—N4	0.1 (3)	C9—C10—C11—C12	1.0 (6)
C7—N3—C6—S1	178.79 (17)	C10—C11—C12—C13	−1.6 (6)
N2—N3—C6—S1	0.9 (3)	C11—C12—C13—C14	0.9 (6)
N2—N3—C7—N5	177.6 (3)	C12—C13—C14—C9	0.4 (6)
C6—N3—C7—S2	−178.7 (2)