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A general methodology to access valuable 4-(phenylchalcogenyl)tetrazolo[1,5-a]quinolines was developed by the reaction of 2-azidobenzaldehyde with phenylchalcogenylacetonitriles (sulfur and selenium) in the presence of potassium carbonate (20 mol%) as a catalyst. The reactions were conducted using a mixture of dimethylsulfoxide and water (7:3) as solvent at 80 °C for 4 h. This new methodology presents a good functional group tolerance to electron-deficient and electron-rich substituents, affording a total of twelve different 4-(phenylchalcogenyl)tetrazolo[1,5-a]quinolines selectively in moderate to excellent yields. The structure of the synthesized 4-(phenylselanyl)tetrazolo[1,5-a]quinoline was confirmed by X-ray analysis.

Herein we present an alternative and transition-metal-free procedure to access 3-organoselanylthiochromones and 3-organoselanylchromones from the cyclization reaction between alkynyl aryl ketones and diorganyl diselenides promoted by Oxone®.

A new method was developed for the synthesis of 4-chalcogenyl-1H-isochromen-1-ones through the 6-endo-dig electrophilic cyclization of 2-alkynylaryl esters and diorganyl dichalcogenides under ultrasound irradiation. The reactions were performed under mild conditions, using Oxone as a green oxidant to promote the cleavage of the chalcogen-chalcogen bond in diorganyl diselenides and ditellurides to generate electrophilic species in situ. A total of 25 compounds were selectively obtained after 30-70 min, in good to excellent yields (74-95%). This procedure was extended to prepare 5H-selenopheno[3,2-c]isochromen-5-ones. Additionally, for the first time, the 4-chalcogenyl-1H-isochromen-1-ones were used as substrates in the thionation reaction, using Lawesson's reagent and microwave irradiation under solvent-free conditions, obtaining the thio derivatives in yields of up to 99% in only 15 min.

We describe our results for the synthesis of 2′-(1,2,3-triazoyl)-acetophenones by copper catalyzed azide–alkyne cycloaddition of 2′-azidoacetophenone with alkynes. The corresponding 2′-(1,2,3-triazoyl)-acetophenones were obtained in moderate to excellent yields and according to our experiments, it was observed that ultrasound accelerates the reaction compared to conventional heating. In addition, the obtained compounds were screened by molecular docking for their possible inhibitory effect on the activity of monoamine oxidase (MAO), an enzyme responsible for the degradation of monoamine neurotransmitters. Three compounds were selected and presented an inhibitory effect on both MAO-A and B isoform activities in vitro. These new MAO inhibitors may be of interest to treat monoamine deficit related-neuropsychiatric disorders, such as depression and Parkinson's disease.

We describe herein an alternative and transition-metal-free procedure for the access of benzo[b]chalcogenophenes fused to selenophenes via intramolecular cyclization of 1,3-diynes. This efficient protocol involves a double cyclization of 1,3-diynyl chalcogen derivatives promoted by the electrophilic species of organoselenium generated in situ by the oxidative cleavage of the Se-Se bond of dibutyl diselenide using Oxone® in acetonitrile as solvent in an open-flask at 80 °C. In this study, 15 selenophenes with broad substrate scope were prepared in moderate to excellent yields (55-98%) with short reaction times (0.5-3.0 h).

We report herein an alternative method for the synthesis of seleno-dibenzocycloheptenones and seleno-spiro[5.5]trienones through the radical cyclization of biaryl ynones in the presence of diorganyl diselenides, using Oxone as a green oxidizing agent. The reactions were conducted using acetonitrile as the solvent in a sealed tube at 100 °C. The protocol is operationally simple and scalable, exhibits high regioselectivity, and allows the synthesis of 24 dibenzocycloheptenones/spiro[5.5]trienones in yields of up to 99%, 17 of which are unpublished compounds. Additionally, synthetic transformations of the prepared compounds, such as oxidation and reduction reactions, are demonstrated.

Pyrazoles represent a significant class of heterocyclic compounds that exhibit pharmacological properties. The present study aimed to investigate the antioxidant potential of pyrazol derivative compounds in brain of mice in vitro and the effect of pyrazol derivative compounds in the oxidative damage and toxicity parameters in mouse brain and plasma of mice. The compounds tested were 3,5-dimethyl-1-phenyl-4-(phenylselanyl)-1H-pyrazol (1a), 3,5-dimethyl-4-(phenylselanyl)-1H-pyrazole (2a), 4-((4-methoxyphenyl)selanyl)-3,5-dimethyl-1-phenyl-1H-pyrazole (3a), 4-((4-chlorophenyl)selanyl)-3,5-dimethyl-1-phenyl-1H-pyrazole (4a), 3,5-dimethyl-1-phenyl-4-(phenylthio)-1H-pyrazole (1b), 3,5-dimethyl-4-(phenylthio)-1H-pyrazole (2b), 4-((4-methoxyphenyl)thio)-3,5-dimethyl-1-phenyl-1H-pyrazole (3b), 4-((4-chlorophenyl)thio)-3,5-dimethyl-1-phenyl-1H-pyrazole (4b), and 3,5-dimethyl-1-phenyl-1H-pyrazole (1c). In vitro, 4-(arylcalcogenyl)-1H-pyrazoles, at low molecular range, reduced lipid peroxidation and reactive species in mouse brain homogenates. The compounds also presented ferric-reducing ability as well nitric oxide-scavenging activity. Especially compounds 1a, 1b, and 1c presented efficiency to 1,1-diphenyl-2-picryl-hydrazyl-scavenging activity. Compounds 1b and 1c presented 2,20 -azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)-scavenging activity. In vivo assays demonstrated that compounds 1a, 1b, and 1c (300 mg/kg, intragastric, a single administration) did not cause alteration in the of δ-aminolevulinic acid dehydratase activity, an enzyme that exhibits high sensibility to prooxidants situations, in the brain, liver, and kidney of mice. Compound 1c reduced per se the lipid peroxidation in liver and brain of mice. Toxicological assays demonstrate that compounds 1a, 1b, and 1c did not present toxicity in the aspartate aminotransferase, alanine aminotransferase, urea, and creatinine levels in the plasma. In conclusion, the results demonstrated the antioxidant action of pyrazol derivative compounds in in vitro assays. Furthermore, the results showed low toxicity of compounds in in vivo assays.

We described here our results on the use of thiourea as a ligand in the copper catalysed azide-alkyne cycloaddition (CuAAC) of 2-azidobenzaldehyde with alkynes. Reactions were performed reacting 2-azidobenzaldehyde with a range of terminal alkynes using 10 mol % of copper iodide as a catalyst, 20 mol % of thiourea as a ligand, triethylamine as base, DMSO as solvent at 100 °C under nitrogen atmosphere. The corresponding 2-(1H-1,2,3-triazoyl)-benzaldehydes (2-TBH) were obtained in moderated to excellent yields and according our experiments, the use of thiourea decreases the formation of side products. The obtained compounds were screened for their binding affinity with multiple therapeutic targets of AD by molecular docking: β-secretase (BACE), glycogen synthase kinase (GSK-3β) and acetylcholinesterase (AChE). The three compounds with highest affinity, 5 a (2-(4-phenyl-1H-1,2,3-triazol-1-yl)benzaldehyde), 5 b (2-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)benzaldehyde), and 5 d (2-(4-(4-(tert-butyl)phenyl)-1H-1,2,3-triazol-1-yl)benzaldehyde) were selected and evaluated on its antioxidant effect, in view of select the most promising one to perform the in vivo validation. Due the antioxidant potential ally to the affinity with BACE, GSK-3β and AChE, compound 5 b was evaluated in a mouse model of AD induced by intracerebroventricular injection of streptozotocin (STZ). Our results indicate that 5 b (1 mg/kg) treatment during 20 days is able to reverse the cognitive and memory impairment induced by STZ trough the modulation of AChE activity, amyloid cascade and GSK-3β expression.

4-(Arylchalcogenyl)-1H-pyrazoles containing selenium or sulfur (0.001–50 mg/kg) were investigated regarding the intragastric route effect (ig) administration on nociception in mice. In this study, nociception and inflammation were induced by chemical agents such as formalin (0.92%), sodium l-glutamate 1-hydrate (20 μmol), croton oil (2.5%), acetic acid (1.6%) and thermic model with a hot plate test. Compounds 1a–c had the ability to reduce licking time in both phases (neurogenic and inflammatory) of the formalin test and glutamate. Only compounds 1a and 1b had the ability to reduce the number of abdominal writhes caused by acetic acid. The same was observed with the positive control celecoxib. To evaluate the possible anti-inflammatory activity of compounds 1a–c, the induction of paw edema by formalin and ear edema by croton oil was performed. For the inflammation induced by formalin, significant effects were observed from the dose of 0.1 mg/kg (1a–b) and 10 mg/kg (1c). In the ear edema test, it can be observed that only compound 1a had a significant effect. In the hotplate test, all the compounds had the ability to reduce the latency time. The results demonstrated that acute antinociceptive and anti-inflammatory effects of 4-(arylchalcogenyl)-1H-pyrazoles 1a is better than compared with the compound 1b and 1c in mice. This resulted in these molecules attracting the interest of researchers to perform future studies to develop new drugs to treat pain and inflammatory clinical conditions.

Polysaccharide-based materials have been claimed as efficient supports for different species used in catalysis, such as transition metal ions. Overall, the immobilization of metal ions on these materials brings several attractive aspects in terms of economy and catalytic activity. In this study, we demonstrated the facile immobilization of Cu2+ ions on alginate-based microspheres (Alg–Cu2+) via a straightforward ion exchange process. The prepared microspheres were characterized in detail by different techniques. As assessed, the ion-exchange process promoted some change in the properties of the microspheres, which was ascribed to the strong interaction forces established between the alginate matrix and Cu2+ ions. The catalytic activity of Alg–Cu2+ was investigated towards the one-pot synthesis of 4-organylselanyl-1H-pyrazole derivatives via cyclocondensation reactions of diketones and hydrazines, followed by direct selenation reactions. In general lines, the starting reagents were efficiently converted via one-pot reactions to different derivatives in moderate to excellent yields. Moreover, the Alg–Cu2+ catalysts still maintained satisfactory catalytic activity even after five consecutive runs. These results indicate that the Alg–Cu2+ microspheres prepared in this study are a promising heterogeneous catalytic system for the synthesis of this class of substituted pyrazoles.

Essential oils (EO) are plant extracts widely used for various pharmacological applications and their antioxidant and anti-inflammatory effects have received a lot of attention because they hold the potential to reduce oxidative stress, and neuroinflammation, alterations involved in the pathophysiology of major depressive disorder. This study examined the benefits of administration of flower EO of the Tagetes minuta (10 and 50 mg/kg, intragastric route) in attenuating behavioral, neurochemical, and neuroendocrine changes in animal models of depressive-like behavior induced by acute restraint stress and lipopolysaccharide (0.83 mg/kg, intraperitoneally). We demonstrated that the treatment of mice with flower EO of the T. minuta reversed the depressive-like behavior induced by stress or inflammatory challenge in mice. This effect is most likely due to the reversal of oxidative stress in the hippocampus of mice, the decrease in plasma corticosterone levels, and restoration of the mRNA levels of brain-derived neurotrophic factor, phosphatidylinositol-3-kinase, protein kinase B, and extracellular signal-regulated kinase 2. As an outcome, flower EO of the T. minuta has promising antidepressant properties and could be considered for new therapeutic strategies for major depressive disorder.

Two new Cu(II) complexes based on 4-(arylchalcogenyl)-1H-pyrazoles monodentate bis(ligand) containing selenium or sulfur groups (2a and 2b) have been synthesized and characterized by IR spectroscopy, high-resolution mass spectrometry (HRMS), and by X-ray crystallography. In the effort to propose new applications for the biomedical area, we evaluated the antioxidant activity and cytotoxicity of the newly synthesized complexes. The antioxidant activity of the Cu(II) complexes (2a - 2b) were assessed through their ability to inhibit the formation of reactive species (RS) induced by sodium azide and to scavenge the synthetic radicals 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS

We describe here our results from the copper-catalyzed three component reaction of 2-azidobenzaldehyde, anthranilamide and terminal alkynes, using Et3N as base, and DMSO as solvent. Depending on the temperature and amount of Et3N used in the reactions, 1,2,3-triazolyl-quinazolinones or 1,2,3-triazolyl-dihydroquinazolinone could be obtained. When the reactions were performed at 100 °C using 2 equivalents of Et3N, 1,2,3-triazolyl-dihydroquinazolinone was formed in 82% yield, whereas reactions carried out at 120 °C using 1 equivalent of Et3N provided 1,2,3-triazolyl-quinazolinones in moderate-to-good yields.

A peroxide-mediated protocol for the synthesis of 2-substituted benzothiazoles was developed, starting from bis(o-aminophenyl) disulfides and primary alcohols. Eleven differently 2-substituted benzothiazoles were prepared in moderate to excellent yields using di-tert-butyl peroxide (DTBP) as an oxidant.

A simple and efficient method for the synthesis of 4‑organoselanyl-1H-pyrazoles has been developed, taking place under metal- and halogen-free conditions. Electrophilic species of selenium were easily generated in situ by the reaction of diorganyl diselenides with Oxone® in ethanol as solvent in an open-flask at 70 °C. These electrophilic selenium species were employed in the selenylation/cyclization of α,β-alkynyl hydrazones, giving the title compounds in moderate to excellent yields. The final species of selenium obtained from the reaction of diphenyl diselenide with Oxone® were characterized by 77Se NMR spectroscopy and high-resolution mass spectrometry (HRMS).

A general methodology to access valuable 3-arylquinoxalin-2(1H)-ones was developed, by the reaction of α-keto acids with ortho-phenylenediamines in the presence of ammonium niobium oxalate (ANO) as a catalyst. The reactions were conducted in only 10 min under ultrasonic irradiation as an alternative energy source, affording water as the only co-product. A total of twenty-three different 3-arylquinoxalin-2(1H)-ones were selectively obtained in good to excellent yields by this atom-efficient protocol. Additionally, 1H–15N HMBC experiments were used to reveal the regioisomerism of the obtained products.

The derivatization of chitosan (CS) is widely exploited to endow this polysaccharide with enhanced physicochemical and biological properties. Beyond the synthetic route, the nature of the compounds used to functionalize the CS-derivatives exerts a pivotal role in their final properties. Making use of a simple “click” reaction, we synthesized for the first time an organoselenium-CS derivative through a 1,2,3-triazole formation. The product (CS-TSe) was characterized in detail by FTIR, NMR (1H, 13C, and 77Se) and UV–Vis techniques, and SEM microscopy. The antioxidant activity of CS-TSe was examined by ABTS+ and DPPH (free radical-scavenging) assays. Experimentally, it was demonstrated that CS-TSe has superior antioxidant activity compared with raw CS and “free” organoselenium compound, suggesting a benign and synergistic effect due to the derivatization. In short, the antioxidant property of CS-TSe combined with the other attractive properties of CS and selenium could be useful in the formulation of advanced materials for biomedical and packaging applications.

This review presents the recent advances involving several applications of five-membered cyclic carbonates and derivatives. With more than 150 references, it covers the period from 2012 to 2020, with special emphasis on the use of five-membered cyclic carbonates as building blocks for organic synthesis and material elaboration. We demonstrate the application of cyclic carbonates in several important chemical transformations, such as decarboxylation, hydrogenation, and transesterification reactions, among others. The presence of cyclic carbonates in molecules with high biological potential is also displayed, together with the importance of these compounds in the preparation of materials such as urethanes, polyurethanes, and flame retardants.

A new method was developed for the synthesis of 4-chalcogenyl-1

Indazoles are fused azaheterocycles with wide applicability in the medical field. In the last decades, the pharmacology interest in this nucleus has increased due to a variety of compounds that show biological activities. Among them are antipyretic, analgesic, anti-inflammatory, antimicrobial, anti-HIV, anti-hypertensive, anti-tumour, anti-fungal and lately is used as an inhibitor of bacterial β-gyrase and a selective estrogen receptor. In addition, organochalcogen compounds have been widely explored due to their possible use as biologically active agents, or as key intermediates and catalysts in organic synthesis. Based on this and due to our continuous interest in the preparation of nitrogen-functionalized organochalcogen compounds, we describe herein our results on the synthesis of 3-(arylselanyl)- and (arylsulfenyl)-2H-indazoles by molecular iodine-catalyzed. Through the reaction of 2H-indazoles and a diverse range of diorganyl diselenides and diorganyl disulfates using catalytic amount of I2 (5 mol%) in DMSO (3.0 equiv.) as oxidant at 100 °C. This protocol proved to be simple, efficient and highly chalcogenated regioselectively at the C3 position to furnish a range of corresponding products selectively substituted 3-(organochalcogenyl)-2H-indazoles. A total of 15 examples were synthesized in good to excellent yields (36 to 98 % ). The products were obtained through a solvent and metal free methodology under mild conditions.

The contribution of oxidative stress has been described in numerous studies as one of the main pathways involved in the pathophysiology of anxiety and its comorbidities, such as chronic pain. Therefore, in this study, we investigated the anxiolytic-like, antiallodynic, and anti-hyperalgesic effects of 3,5-dimethyl-1-phenyl-4-(phenylselanyl)-1H-pyrazole (SePy) in response to acute restraint stress (ARS) in mice through the modulation of oxidative stress and neuroendocrine responses. Mice were restrained for 2 h followed by SePy (1 or 10 mg/kg, intragastrically) treatment. Behavioral, and biochemical tests were performed after further 30 min. The treatment with SePy reversed (i) the decreased time spent and the number of entries in the open arms of the elevated plus-maze apparatus, (ii) the decreased time spent in the central zone of the open field test and the increased number of grooming, (iii) the increased number of marbles buried, (iv) the increased response frequency of Von Frey Hair stimulation, and (v) the decreased latency time to nociceptive response in the hot plate test stress induced by ARS. Biochemically, SePy reversed ARS-induced increased levels of plasma corticosterone, and reversed the ARS-induced alterations in the levels of reactive species, lipid peroxidation, and superoxide dismutase and catalase activities in the prefrontal cortices and hippocampi of mice. Moreover, a molecular docking approach suggested that SePy may interact with the active site of the glucocorticoid receptor. Altogether, these results indicate that SePy attenuated anxiolytic-like behavior, hyperalgesia, and mechanical allodynia while modulating oxidative stress and neuroendocrine responses in stressed mice.

Here, we report the general strategies by which NMR spectroscopy can be used to determine the enantiopurity and absolute configuration of chalcogen containing secondary alcohols, including the evaluation of the use of chiral solvating and chiral derivatizing agents. The BINOL/DMAP ternary complex demonstrated a simple and fast protocol for determining enantiopurity. The drug Naproxen afforded a stable, nonhygroscopic, and readily available chiral derivatizing agent (CDA) for NMR chiral discrimination of chalcogen containing secondary alcohols. The chiral recognition by CDA and chiral solvating agent (CSA) was assessed using 1 H, 77 Se-{1H}, and 125 Te-{1H} NMR spectroscopy. A simple model for the assignment of the absolute configuration from NMR data is presented.

A one-pot iodine-catalyzed multicomponent reaction has been developed for the selective preparation of 5-amino-4-(arylselanyl)-1H-pyrazoles from a diverse array of benzoylacetonitriles, arylhydrazines and diaryl diselenides. The reactions were conducted in MeCN as solvent at reflux temperature under air. The methodology presents a large functional group tolerance to electron-deficient, electron-rich, and bulky substituents and gave the expected products in good to excellent yields. The synthesized 1,3-diphenyl-4-(phenylselanyl)-1H-pyrazol-5-amine was submitted to an oxidative dehydrogenative coupling to produce a diazo compound confirmed by X-ray analysis.