Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones.

The broad application of 1H-indazoles has prompted the development of several approaches for the synthesis of such compounds, including metal-free, palladium-, or copper-promoted intramolecular N-arylation of in situ-generated or isolated o-haloarylhydrazones. Such methods mainly start from o-bromo derivatives due to the better yield observed when compared to those obtained from o-chloroarylhydrazones. However, the o-chloroarylaldehydes and o-chloroarylketones used to prepare the arylhydrazones are more commercially available and less expensive than brominated analogs. Seeking to cover a lack in the literature, this work reports a convenient protocol for the synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of o-chlorinated arylhydrazones. Therefore, a series of seven N-phenyl derivatives and a series of six novel N-thiazolyl derivatives was obtained in 10-70% and 12-35% yield, respectively, after stirring the o-chlorinated arylhydrazones, CuI, KOH, and 1,10-phenantroline for 12-48 hours in DMF at 120 °C. The products were isolated by column chromatography on silica gel. All products were fully characterized by HRMS as well as 1H and 13C NMR spectroscopy. Thus, this approach is valuable for promoting the synthesis of N-phenyl-1H-indazoles in a higher yield than that reported in the literature using copper catalysis and the same substrates. This study also prompted the first reported synthesis of pharmacologically interesting N-thiazolyl derivatives.

Co(II), Ni(II), and Zn(II) complexes based on new hybrid imine-pyrazole ligands: structural, spectroscopic, and electronic properties.

The present work reports the theoretical investigation of Co(II), Ni(II), and Zn(II) complexes containing Schiff bases (used as ligands) derived from the reaction of 2-hydroxy-1-naphthaldehyde with N-(2-aminoethyl) pyrazoles. The spectral analyses were carried out using infrared, Raman, and UV-Vis spectroscopy. Vibrational analyses were performed in order to investigate the mechanisms involving metal-ligand and intra-ligand vibrations and indicated the possibility of charge transfer related to the transitions n[Formula: see text]* and [Formula: see text]*. Structure optimizations and normal coordinate force field calculations were performed via the density functional theory (DFT) method at the HSE06/6-311G(d,p)/LanL2DZ level. A thorough analysis was also conducted regarding the nonlinear optical (NLO) properties and the natural bond orbital (NBO) of the complexes. The results show that these complexes have prospective application as materials for NLO. Furthermore, the NBO analysis confirms the coordination between the lone pair (LP) electrons of the donor atoms (O and N) and the metal acceptors. Finally, studies were conducted regarding the electronic properties of the complexes; among the properties investigated included the frontier molecular orbitals (FMO) and the molecular electrostatic potential (MEP), allowing to determine the energy gap and charge distribution.

In silico toxicity evaluation for transformation products of antimicrobials, from aqueous photolysis degradation.

This study investigates degradation processes of three antimicrobials in water (norfloxacin, ciprofloxacin, and sulfamethoxazole) by photolysis, focusing on the prediction of toxicity endpoints via in silico quantitative structure-activity relationship (QSAR) of their transformation products (TPs). Photolysis experiments were conducted in distilled water with individual solutions at 10 mg L-1 for each compound. Identification of TPs was performed by means of LC-TOF-MS, employing a method based on retention time, exact mass fragmentation pattern, and peak intensity. Ten main compounds were identified for sulfamethoxazole, fifteen for ciprofloxacin, and fifteen for norfloxacin. Out of 40 identified TPs, 6 have not been reported in the literature. Based on new data found in this work, and TPs already reported in the literature, we have proposed degradation pathways for all three antimicrobials, providing reasoning for the identified TPs. QSAR risk assessment was carried out for 74 structures of possible isomers. QSAR predictions showed that all 19 possible structures of sulfamethoxazole TPs are non-mutagenic, whereas 16 are toxicant, 18 carcinogenic, and 14 non-readily biodegradable. For ciprofloxacin, 28 out of the 30 possible structures for the TPs are mutagenic and non-readily biodegradable, and all structures are toxicant and carcinogenic. All 25 possible norfloxacin TPs were predicted mutagenic, toxicant, carcinogenic, and non-readily biodegradable. Results obtained from in silico QSAR models evince the need of performing risk assessment for TPs as well as for the parent antimicrobial. An expert analysis of QSAR predictions using different models and degradation pathways is imperative, for a large variety of structures was found for the TPs.