A simple and efficient synthesis of N-[3-chloro-4-(4-chlorophenoxy)-phenyl]-2-hydroxy-3,5-diiodobenzamide, rafoxanide.

A method for the synthesis of rafoxanide 6, a halogenated salicylanilide used as an efficient anthelmintic in sheep and cattle, is presented. Rafoxanide 6 was synthesized in only three steps from readily available 4-chlorophenol with 74% overall yield. The synthesis has two key stages: the first was salicylic acid iodination, adding iodine in the presence of hydrogen peroxide, which allowed obtaining a 95% yield. The second key stage was the reaction of 3,5-diiodosalicylic acid 5 with aminoether 4, where salicylic acid chloride was formed in situ with PCl3 achieving 82% yield. Chemical characterization of both intermediates and final product was achieved through physical and spectroscopic (IR, NMR and MS) techniques. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-023-02846-9.

Ligand influence in electrocatalytic properties of Cu(II) triazole complexes for hydrogen peroxide detection in aqueous media.

In this work, electrocatalytic changes of Cu(II) triazole complexes (Cu(L)2) resulting from inductive effects were evaluated to fabricate a sensor for hydrogen peroxide (H2O2) determination. Three copper(II) complexes with electronically differentiated ligands were synthesized by slow diffusion method and characterized by X-ray crystallography, Fourier transformed infrared (FTIR), UV-Vis, scanning electron microscopy (SEM) and voltammetry cyclic (CV). Cu(LOMe)2/GC, Cu(LBr)2/GC and Cu(LNO2)2/GC sensors were then prepared. Under optimal conditions (pH = 11), the optimal sensor presented a response at -0.5 V, good linear range of 1-32 µM, reproducibility (1.7%), repeatability (1.2%), LOD of 0.0246 µM (S/N = 5), LOQ of 0.0747 µM (S/N = 5) and selectivity. Additionally, Cu(LNO2)2/GC sensor has been successfully applied in commercial substances, such as mouthwash, milk and tea.

Synthesis, antitumor activity, 3D-QSAR and molecular docking studies of new iodinated 4-(3H)-quinazolinones 3N-substituted.

A novel series of 6-iodo-2-methylquinazolin-4-(3H)-one derivatives, 3a-n, were synthesized and evaluated for their in vitro cytotoxic activity. Compounds 3a, 3b, 3d, 3e, and 3h showed remarkable cytotoxic activity on specific human cancer cell lines when compared to the anti-cancer drug, paclitaxel. Compound 3a was found to be particularly effective on promyelocytic leukaemia HL60 and non-Hodgkin lymphoma U937, with IC50 values of 21 and 30 µM, respectively. Compound 3d showed significant activity against cervical cancer HeLa (IC50 = 10 µM). The compounds 3e and 3h were strongly active against glioblastoma multiform tumour T98G, with IC50 values of 12 and 22 µM, respectively. These five compounds showed an interesting cytotoxic activity on four human cancer cell types of high incidence. The molecular docking results reveal a good correlation between experimental activity and calculated binding affinity on dihydrofolate reductase (DHFR). Docking studies proved 3d as the most potent compound. In addition, the three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis exhibited activities that may indicate the existence of electron-withdrawing and lipophilic groups at the para-position of the phenyl ring and hydrophobic interactions of the quinazolinic ring in the DHFR active site.

2-(4-Bromo-phen-yl)-N-[3-(1H-imidazol-1-yl)prop-yl]quinazolin-4-amine.

In the title compound, C(20)H(18)BrN(5), the bromo-phenyl-substituted quinazoline unit is essentially planar [maximum deviation = 0.098 (3) Å] and makes a dihedral angle of 56.04 (14)° with the imidazole ring. In the crystal, mol-ecules are associated by pairs of N-H⋯N hydrogen bonds to form inversion dimers. All the quinazoline planar systems are oriented almost perpendicular to the [110] direction, making π-π inter-actions possible between adjacent dimers [centroid-centroid distances = 3.7674 (16) and 3.7612 (17) Å]. There are also a number of C-H⋯π inter-actions present. The crystal is a nonmerohedral twin, with a minor twin fraction of 0.47.

1-(2,4-Difluoro-phen-yl)-2-(1H-1,2,4-triazol-1-yl)ethanol.

In the title compound, C(10)H(9)F(2)N(3)O, the dihedral angle between the mean planes of the triazole and benzene rings is 20.6 (2)°. In the crystal, mol-ecules are linked by strong O-H⋯ N hydrogen bonds into chains with graph-set notation C(9) along [100]. Weak C-H⋯N and C-H⋯F inter-actions are also observed.

2-Amino-N'-phenyl-benzohydrazide.

In the title compound, C(13)H(13)N(3)O, the NNCO unit forms dihedral angles of 35.8 (1) and 84.0 (1)° with the benzene and phenyl rings, respectively. The dihedral angles between the aromatic rings is 61.2 (1)°. An intra-molecular N-H⋯O hydrogen bond occurs. In the crystal, mol-ecules are linked by weak N-H⋯O hydrogen bonds into C(4) chains parallel to the c axis. Neighbouring chains are linked by weak N-H⋯N hydrogen bonds, forming R(4) (4)(20) rings, and resulting in the formation of a two-dimensional network lying parallel to (010). The packing also features π-π stacking inter-actions between phenyl rings [centroid-centroid distance = 3.803 (2) Å].