Succinct and Facile Synthesis of Innovative Thiopyrimidines With Antimicrobial and Antitubercular Investigation

Abstract

To develop a series of bioactive heterocycles in minimum number of steps, 3-methyl- 4-(substituted phenyl)-1-phenyl-4,8-dihydropyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidine-5,7 (1H,6H)-dithione 2(a–j), 4-(4-substituted phenyl)-5-imino-3-methyl-1,6-diphenyl-4,5,6,8-tetrahydropyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidine-7(1H)-thione 3(a–j), and N-[4-(subs- tituted phenyl)-3-methyl-1-phenyl-7-thioxo-1,4,7,8-hexahydropyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidine-5-yl]thiourea 4(a–j) have been synthesized from amino nitrile functionality 1(a–j). The structures of the compounds were elucidated by IR, ¹H NMR, elemental analysis, and some representative ¹³C NMR and mass spectra. All the title compounds were screened for antimicrobial and antitubercular activities, while some representative compounds were tested for antioxidant activity. Out of synthesized compounds, compounds 1j (4-CH₃), 2d (4-F), 4c (4-OH), and 4i (3-Br) exhibited maximum inhibition against Mycobacterium Tuberculosis H₃₇Rv. Compound 3c (4-OH) revealed elevated efficacy against all tested bacterial strain, while compounds 1i (3-Br), 2c (4-OH), and 3h (3-NO₂) were found efficacious against Candida albicans as compared to standard drugs.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Synthesis and Complexing Properties of Novel Crown Ethers and Thiacrown Ethers Incorporating New Heterocyclic Moieties

The synthesis of some novel crown and thiacrown ethers via the reaction of 2,3-bis(4-hydroxyphenyl) or 2,3-bis(4-mercaptophenyl)quinoxalines and pyridopyridazine with diethylene and triethylene glycol ditosylate is described. The complexing ability of compounds 5b and 5h, as the representatives of both groups of compounds, with alkali and alkali earth metal cations were measured by the solvent extraction method. The results showed that crown ether 5b comparatively had more affinity towards the Mg²⁺ cation, while thiacrown ether 5h had greater affinity towards the Ca²⁺ cation.     

Earth Alkaline Tetrathiosquarates. II. – Syntheses and Crystal Structures of SrC4S4·4 H2O and Ba4K2(C4S4)5·16 H2O

Concentrated aqueous solutions of strontium chloride and barium chloride, respectively, allow on addition of the potassium salt of tetrathiosquarate, K₂C₄S₄·H₂O, the isolation of the earth alkaline salts SrC₄S₄·4 H₂O ( 1 ) and Ba₄K₂(C₄S₄)₅·16 H₂O ( 2 ), both as dark red crystals. The crystal structure determinations ( 1 : orthorhombic, Pnma, a = 8.149(1), b = 12.907(2), c = 10.790(2) Å, Z = 4; 2 : orthorhombic, Pbca, a = 15.875(3), b = 21.325(5), c = 16.119(1) Å, Z = 4) show the presence of C₄S₄²⁻ ions with only slightly distorted D_4h symmetry having average C–C and C–S bond lengths of 1.41Å and 1.681Å for 1 and 1.450Å and 1.657Å for 2 . The structure of 1 contains concatenated edge‐sharing Sr(H₂O)₆S₂ polyhedra. The Sr²⁺ ions are in eight‐fold coordination with Sr–O distances of 2.50–2.72Å and Sr–S distances of 3.21Å, (C₄S₄)²⁻ acts as a chelating ligand towards Sr²⁺. The structure is closely related to the previously reported Ca²⁺ containing analogue, which is of lower symmetry belonging to the monoclinic crystal system. A supergroup‐subgroup relation between the space groups of both structures is present. The structure of 2 is made up of Ba²⁺ and K⁺ ions in eight and nine‐fold coordination by H₂O molecules and (C₄S₄)²⁻ ions which act as chelating ligands towards one cation and bridging between two cations. The coordination polyhedra of the cations are connected by common edges and corners in two dimensions to layers which are connected by tetrathiosquarate ions to a three‐dimensional network. The infrared and Raman spectra show bands typical for the molecular building units of the two compounds.     

Earth Alkaline Tetrathiosquarates: Syntheses and Crystal Structures of MgC4S4 · 6 H2O and CaC4S4 · 4 H2O

Concentrated aqueous solutions of magnesium chloride and calcium nitrate, respectively, allow on addition of the potassium salt of tetrathiosquarate, K₂C₄S₄ · H₂O, the isolation of the earth alkaline salts MgC₄S₄ · 6 H₂O ( 1 ) and CaC₄S₄ · 4 H₂O ( 2 ) as orange and red crystals. The crystal structure determinations ( 1 : monoclinic, C2/c, a = 17.2280(7), b = 5.9185(2), c = 13.1480(4) Å, β = 104.730(3)°, Z = 4; 2 : monoclinic, P2₁/m, a = 7.8515(3), b = 12.7705(5), c = 10.6010(4) Å, β = 93.228(2)°, Z = 4) show the presence of C₄S₄^2? ions with almost undistorted D_4h symmetry having average C–C and C–S bond lengths of 1.451Å and 1.659Å for 1 and 1.451Å and 1.655Å for 2 . The structure of 1 contains discrete, octahedral [Mg(H₂O)₆]²⁺ complexes. Several O–H····O and O–H····S bridges with H····O and H····S distances of less than 2.50Å connect cations and anions. The structure of 2 is built of concatenated, edge‐sharing Ca(H₂O)₆S₂ polyhedra. The Ca²⁺ ions have the coordination number eight, C₄S₄^2? act as a chelating ligands towards Ca²⁺ with Ca–S distances of 3.14Å. The infrared and Raman spectra show bands typical for the molecular building units of the two compounds.     

Spectrophotometric and derivative spectrophotometric determination of palladium(II) using pyridopyridazine dithione in the presence of non-ionic surfactant

Pyridopyridazine dithione (PPD) was synthesized as a new sensitive and selective reagent for spectrophotometric and derivative spectrophotometric determination of palladium(II). In aqueous and micellar medium, PPD forms 1:4 complexes having molar absorptivities of 4.68 × 10⁴ and 5.74 × 10⁴lmol^–1 cm^–1 at 570 and 615 nm, respectively. Beer's law was obeyed up to 2.2 and 2.5 g ml^–1 with detection limits of 0.2 and 0.1g ml^–1. The relative standard deviations for 1.23g ml^–1 were 2.6 and 1.3%, in the absence and presence of Triton X-100. In fourth-derivative mode, the regression equation, linear range, detection limit and RSD for 0.075 g ml^–1 wereD ₄ = 4.3C + 1.5 × 10^–3, 0.013 – 0.23 g ml^–1, 3.7 ng ml–1 and 0.78%, respectively. The ionization constants of the reagent and stability constants of the complexes were evaluated. The method is free from interference by most common metal ions and anions. The method was applied for determination of palladium in activated charcoal.