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

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.


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 1,2,4triazole 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-1,2,4triazole [1.371 Å (Borbulevych et al., 1998)], because the latter contains an electron-withdrawing CF 3 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).
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.

Refinement
All H atoms were placed in calculated positions, with C-H=0.93-0.97 Å, and included in the final cycles of refinement using a riding model, U iso (H) = 1.2U eq (C). Fig. 1. The molecular structure of the title compound with the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.