Ethyl 5-[6-(furan-2-yl)-1,2,4-triazolo[3,4-b][1,3,4]thia­diazol-3-yl]-2,6-di­methylnicotinate

Dongliang Lu; Min Zhang; Liping Song; Qiwen Tan; Min Shao

doi:10.1107/S1600536807061144

. 2007 Dec 6;64(Pt 1):o80–o81. doi: 10.1107/S1600536807061144

Ethyl 5-[6-(furan-2-yl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazol-3-yl]-2,6-dimethylnicotinate

Dongliang Lu ^a, Min Zhang ^a,^*, Liping Song ^a, Qiwen Tan ^a, Min Shao ^b

PMCID: PMC2915037 PMID: 21200958

Abstract

In the title compound, C₁₇H₁₅N₅O₃S, the plane of the triazolo–thiadiazole system forms dihedral angles of 15.68 and 4.46° with the planes of the pyridine and furan rings, respectively. In the molecule, there is an intramolecular C—H⋯N interaction. The crystal structure also contains other intermolecular interactions, such as C—H⋯O hydrogen bonds, π–π stacking (centroid–centroid distances = 3.746 and 3.444 Å), non-bonded S⋯N [3.026 (2) Å] and C—H⋯π interactions.

Related literature

For related literature, see: Borbulevych et al. (1998 ▶); Bruno et al. (2003 ▶); Collin et al. (2003 ▶); Cooper & Steele (1990 ▶); Dinçer et al. (2005 ▶); Golgolab et al. (1973 ▶); Holla et al. (1994 ▶, 1998 ▶, 2002 ▶); Lu et al. (2007 ▶); Shen et al. (2006 ▶); Tsukuda et al. (1998 ▶); Wagner et al. (2005 ▶); Witkoaski et al. (1972 ▶); Zhang & Wen (1998 ▶); Özbey et al. (2000 ▶).

Experimental

Crystal data

C₁₇H₁₅N₅O₃S
M _r = 369.40
Triclinic,
a = 8.094 (4) Å
b = 10.535 (5) Å
c = 10.996 (5) Å
α = 66.699 (5)°
β = 73.683 (5)°
γ = 80.998 (5)°
V = 825.4 (7) Å³
Z = 2
Mo Kα radiation
μ = 0.23 mm⁻¹
T = 296 (2) K
0.30 × 0.30 × 0.25 mm

Data collection

Bruker SMART CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.935, T _max = 0.946
4297 measured reflections
2860 independent reflections
2531 reflections with I > 2σ(I)
R _int = 0.017

Refinement

R[F ² > 2σ(F ²)] = 0.038
wR(F ²) = 0.100
S = 1.06
2860 reflections
235 parameters
H-atom parameters constrained
Δρ_max = 0.22 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Data collection: SMART (Bruker, 2000 ▶); cell refinement: SAINT (Bruker, 2000 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997 ▶); molecular graphics: SHELXTL (Bruker, 2000 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536807061144/av3123sup1.cif

e-64-00o80-sup1.cif^{(17.8KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536807061144/av3123Isup2.hkl

e-64-00o80-Isup2.hkl^{(137.5KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

Cg is the centroid of the furan ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C3—H3⋯N5	0.93	2.31	2.982 (3)	128
C13—H13⋯O2ⁱ	0.93	2.51	3.285 (3)	141
C17—H17A⋯O1ⁱⁱ	0.96	2.56	3.424 (3)	149
C17—H17A⋯Cgⁱⁱⁱ	0.96	3.29	4.008 (3)	134

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

Acknowledgments

The authors thank the Instrument Analysis and Research Center of Shanghai University for the crystal structure analysis.

supplementary crystallographic information

Comment

Antimicrobials reduce or completely block the growth and multiplication of bacteria. This has made them unique for the control of deadly infectious diseases caused by a variety of pathogens. They have transformed our ability to treat infectious diseases such as pneumonia, meningitis, tuberculosis, malaria, and AIDS. Derivatives of 1,2,4-triazole and 1,3,4-thiadiazole condensed nucleus systems are found to have diverse pharmacological activities (Collin et al., 2003) such as fungicidal, insecticidal, bactericidal, herbicidal, anti-tumor (Holla et al., 2002), and anti-inflammatory (Cooper & Steele, 1990), and CNS stimulant properties (Holla et al., 1994). They also find applications as dyes, lubricants and analytical reagents (Zhang & Wen, 1998), antiviral agents (Witkoaski et al., 1972), heterocyclic ligands (Shen et al., 2006). Examples of such compounds bearing the 1,2,4-triazole moieties are fluconazole, a powerful azole antifungal agent (Tsukuda et al., 1998) as well as the potent antiviral N-nucleoside ribavirin (Witkoaski et al., 1972). Also, a number of 1,3,4-thiadiazoles show antibacterial properties similar to those of well known sulfonamide drugs (Golgolab et al., 1973). The thiadiazole nucleus with N—C—S linkage exhibits a large number of biological activities (Holla et al., 1998). Prompted by these findings and in continuation of our efforts in synthesizing some condensed bridge bioactive molecules bearing multifunctional and pharmaceutically active groups, herein, we report a new 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole derivative which has been firstly prepared. In view of these important properties, the present single-crystal X-ray diffraction study of the title compound, (I), was carried out in order to investigate this bicyclic system and to confirm the assigned structure.

Compound (I) (Fig. 1) is composed of a fused triazolo-thiadiazole system, one pyridine ring attached to the triazole ring, the other furan ring is bonded to the thiadiazole ring, respectively. The fused triazolo-thiadiazole ring and furan ring nearly adopt coplanar form due to formation of a large π-π conjugation system. The plane of the triazolo-thiadiazole system forms dihedral angles of 15.68 and 4.46 ° with the planes of the pyridine and furan rings, respectively. Remarkably, the dihedral angle of pyridine and triazole-thiadiazole planes is significantly larger than this in the literature [1.53 ° (Dinçer et al., 2005)]. This should be attributed to the steric hindrance caused by the methyl group at α-position of pyridine ring, resulting in the enlargement of dihedral angle.

Moreover, the bond distance N2—N3 (1.398 (2) Å) is in accordance with those found for structures containing the 1,2,4-triazole ring (Lu et al., 2007; Bruno et al., 2003), indicating that the bond distance N2—N3 is relevant to the resonance effect of fused triazole-thiadizole ring, other than the dihedral angle between the pyridine ring and a fused ring, although two molecules display different dihedral angles. Apparently, it is longer than that of 5-ammo-3-trifluoromethyl-1-H-1,2,4-triazole [1.371 Å (Borbulevych et al., 1998)], because the latter contains an electron-withdrawing CF₃ group attached to the 3-position of the triazole ring. In the thiadiazole moiety, the S1—C10 (1.730 (8) Å) and S1—C11 (1.761 (8) Å) bond distances show the similar pattern as those in the literature (Dinçer et al., 2005). The difference between S1—C10 and S1—C11 indicates that the bond distances mainly depend on the nature of resonance effort caused by fused triazolo-thiadiazole, rather than the aromatic ring attached to the 5-position of thiadiazole ring, because in our case, the aromatic ring is not the phenyl group, but the furan-2-yl group. The bond distances and angles of the furan ring are comparable with those in the literature (Wagner et al., 2005).

In the molecular structure, intramolecular C3—H3···N5 contacts lead to the formation of a five-membered ring fused with the pyridine ring. In addition, the C3—N5 distance is 2.982 (3) Å, a little shorter than that in the literature [3.140 (2)Å Özbey et al., 2000)].

The structure contains two weak π-π stacking interactions. The first of them is between the triazole ring and the thiadiazol ring, its symmetry related partner at (1 - x, -y, 1 - z), with a distance of 3.746 Å between the ring centroids and a perpendicular distance between the rings of 3.444 Å. The second one is between the triazole ring and the pyridine ring at (1 - x, 1 - y, -z), with a distance of 3.701Å between the ring centroids and a perpendicular distance between the rings of 3.541 Å. In addition to these interactions, there are two types of intermolecular hydrogen bonds C13—H13···O2 (1 - x, 1 - y, 1 - z) and C17—H17A···O1(1 - x, -y, 1 - z) which make the crystal structure to be more stable. The hydrogen-bonding geometry is listed in Table 2. Some short-contact distances are not listed in the table. Yet noteworthy, is S1···N3 (1 - x, -y, -z) of 3.026 (2) Å, and a π-ring interaction at (1 + x, y, z) with the distance 3.285 (9) Å between H17A and furan ring, both of them may cause steric hindrance.

Experimental

(1 mmol, 0.293 g)ethyl- 5-(4-amino-5-mercapto-4H-1,2,4-triazol-3-yl) -2,6-dimethylnicotinate, and (1 mmol, 0.112 g) furan-2- carboxylic acid were dissloved in 3.5 ml phosphorous oxychloride. The mixture was refluxed for 4 h, and allowed to cool to room temperature. The reaction mixture was poured into crushed ice, then, neutralized with dilute sodium bicarbonate solution. The solid separated was filtered off, washed with water, dried and recrystallized from chloroform afford pure product in a yield of 86% (m.p. 501–502 K). Single crystals suitable for X-ray analysis were obtained from chloroform by slow evaporation at room temperature. IR(ν, cm^-1): 3101–3001 (Furan CH), 1725 (C=O), 1586–1444 (C=C, C=N), 1270 (C—S—C); ¹H-NMR (500 MHz, CD₃Cl): δ 8.82 (s, 1H, Pyridine CH), 6.67–7.70 (m, 3H, Furan CH), 4.41 (q, J=7.0 Hz, 2H, CH), 2.92 (s, 3H, Pyridine CH), 2.87 (s, 3H, Pyridine CH), 1.42 (t, J=7.0 Hz, 3H, CH);Element analysis, required for C₁₇H₁₅N₅O₃S: C 55.27, H 4.09, N 18.96%; Found: C 55.29, H 4.08, N 18.68%.