Bahgat R. M. Hussein

Synthesis and Antibacterial Activity of Some New S-Triazole Derivatives

Abstract Alkylation of 4-anilino-5-phenyl-4H-1,2,4-triazole-3-thiol (1) with some halo compounds yielded the corresponding sulfides 2a–f. Some sulfides 2e,f were cyclized to give triazolothiadiazines 3 and 4. Triazolothiadiazoles 5 and 6 were prepared through the reaction of compound 1 with carbon disulfide or ethyl orthoformate, respectively. Treatment of compound 1 with ethyl chloroformate or phenyl isothiocyanate yielded triazolo-thiadiazole and triazole 9 and 10, respectively. Reaction of compound 1 with Lawessons reagent gave triazolothiadiazaphosphole derivative 11. Also, compound 1 underwent cyclocondensation reactions with some bidentate reagents to give triazolothiazines 4, 12, and 13. Triazolo-thiazepines and triaziepine 14–16 were synthesized via the reaction of compound 1 with β-ketoesters or ethyl cyanoacetate. Tricyclic systems 19 and 20 were prepared through the reaction of compound 4 with the appropriate reagent. Some synthesized compounds were tested for antibacterial activity. Supplemental materials are available for this article. Go to the publishers online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. GRAPHICAL ABSTRACT

Synthesis, in vitro Antibacterial and in vivo Anti-Inflammatory Activity of Some New Pyridines

Reaction of 4,6-diamino-3-cyano-2-methylthiopyridine (I) with chloroacetyl chloride or acetic acid afforded the corresponding 6-acetamide derivatives IIa and IIb, respectively. Chloroacetamide derivative IIa reacted with various thiols, secondary amines, potassium thiocyanate, compounds containing active methylene group, 1-anilino-2,2-dicyanoethenethiolate, and o-mercatocyanopyridines to give S-alkyl, N-alkyl, thiazole, pyrrole, thiophene, and thienopyridine derivatives, respectively. Antibacterial and anti-inflammatory activities of some new pyridine derivatives were studied.

Crystal structure of N-[4-amino-5-cyano-6-(methyl-sulfan-yl)pyridin-2-yl]-2-chloro-acetamide.

In the title compound, C9H9ClN4OS, the dihedral angle between the acetamide moiety and the pyridine ring is 4.83 (12)°. The O=C—C—Cl torsion angle is 46.4 (3)° and an intramolecular C—H⋯O interaction generates an S(6) ring. In the crystal, molecules are linked by N—H⋯O, N—H⋯N and C—H⋯N hydrogen bonds, generating sheets lying parallel to (120).

Crystal structure of 4,6-di­amino-2-sulfanyl­idene-1,2-di­hydro­pyridine-3-carbo­nitrile

The title compound, C6H6N4S, crystallizes with two independent molecules, A and B, in the asymmetric unit. Both independent molecules are almost planar [maximum deviations of 0.068 (6) Å in molecule A and 0.079 (6) Å in molecule B]. In the crystal, molecules A and B are linked by N—H⋯S, N—H⋯N and C—H⋯S hydrogen bonds, forming a three-dimensional network.

Ethyl 2-[({[4-amino-5-cyano-6-(methyl­sulfan­yl)pyridin-2-yl]carbamo­yl}meth­yl)sulfan­yl]acetate monohydrate

The title compound, C13H16N4O3S2·H2O, crystallizes in a ‘folded’ conformation with the ester group lying over the carbamoyl moiety, with one solvent water molecule. The molecular conformation is stabilized by an intramolecular C—H⋯O hydrogen bond, and an N—H⋯O hydrogen-bonding interaction involving the lattice water molecule. The packing involves N—H⋯N, N—H⋯O, O—H⋯N and O—H⋯O hydrogen bonds and consists of tilted layers running approximately parallel to the c axis, with the ester groups on the outer sides of the layers and with channels running parallel to (101).

Crystal structure of 4,6-di-amino-2-(methyl-sulfan-yl)pyridine-3-carbo-nitrile.

The title pyrimidine derivative, C7H8N4S, is essentially planar, with a maximum deviation of 0.029 (2) Å from the mean plane of the non-H atoms. In the crystal, molecules are linked by an intermolecular bifurcated N—H⋯N hydrogen bond between the cyano N atom and the two amino groups, an N—H⋯N hydrogen bond between the two amino groups and a weak C—H⋯π interaction, forming a three-dimensional network.

Crystal structure of 4,6-diamino-2-(methylsulfanyl)pyridine-3-carbonitrile

The title pyrimidine derivative, C7H8N4S, is essentially planar, with a maximum deviation of 0.029 (2) Å from the mean plane of the non-H atoms. In the crystal, molecules are linked by an intermolecular bifurcated N—H⋯N hydrogen bond between the cyano N atom and the two amino groups, an N—H⋯N hydrogen bond between the two amino groups and a weak C—H⋯π interaction, forming a three-dimensional network.

Crystal structure of N-[4-amino-5-cyano-6-(methyl­sulfan­yl)pyridin-2-yl]acetamide hemihydrate

The title compound, C9H10N4OS·0.5H2O, crystallizes with two independent molecules (A and B) in the asymmetric unit, together with a water molecule of crystallization. The acetamide moiety, which has an extended conformation, is inclined to the pyridine ring by 7.95 (16)° in molecule A and by 1.77 (16)° in molecule B. In the crystal, the A and B molecules are linked by two N—H⋯Ocarbonyl hydrogen bonds, forming a dimer. The dimers are linked via N—H⋯N hydrogen bonds, forming ribbons that are linked by N—H⋯Owater hydrogen bonds to form sheets parallel to (110). The sheets are linked by O—H⋯N hydrogen bonds, forming slabs, and between the slabs there are weak slipped parallel π–π interactions [inter-centroid distance = 3.734 (2) Å, interplanar distance = 3.3505 (11) Å and slippage = 1.648 Å], forming a three-dimensional structure.

Crystal structure of 4,6-diamino-2-(methylsulfanyl) pyridine-3-carbonitrile

The title pyrimidine derivative, C7H8N4S, is essentially planar, with a maximum deviation of 0.029 (2) Å from the mean plane of the non-H atoms. In the crystal, molecules are linked by an intermolecular bifurcated N—H⋯N hydrogen bond between the cyano N atom and the two amino groups, an N—H⋯N hydrogen bond between the two amino groups and a weak C—H⋯π interaction, forming a three-dimensional network.

Crystal structure of N-[4-amino-5-cyano-6-(methyl-sulfan-yl)pyridin-2-yl]-2-(cyclo-hexyl-sulfan-yl)acetamide.

In the title molecule, C15H20N4OS2, the acetamido fragment is nearly coplanar with the pyridyl ring [C—N—C—C torsion angle = −4.1 (2)°], while the cyclohexylsulfanyl portion protrudes from this plane [N—C—C—S torsion angle = −40.8 (6)°]. In the crystal, alternating pairwise N—H⋯O and N—H⋯N hydrogen bonds across inversion centres form chains along [101], which are associated into stepped layers via offset π–π stacking between pyridyl rings [centroid–centroid distance = 3.566 (1) Å]. The cyclohexyl group and the two atoms of the S—C bond attached to it are disordered over two sets of sites with site-occupancy factors of 0.8845 (18) and 0.1155 (18).