Vera L. M. Silva

Role of the Base and Control of Selectivity in the Suzuki–Miyaura Cross‐Coupling Reaction

The outcome of the Suzuki–Miyaura cross‐coupling for the direct competition reaction between two boronic acids was evaluated under routine synthesis conditions. The reaction selectivity was found to depend on the amount of the base used, with fewer bases favoring the reactivity of the boronic acid with lower pKa (stronger acid). The dependence of the reaction selectivity on base stoichiometry was found to increase with the increase in the difference in the pKa values of the competing boronic acids. These results confirm a relationship between acid–base chemistry and the Suzuki–Miyaura reaction catalytic cycle. Moreover, the results indicate that under these specific conditions, the most reactive organoboron species toward transmetalation is the borate anion RB(OH)3− instead of the neutral boronic acid RB(OH)2. Hence, the main role of the base in the reaction mechanism is to increase the reactivity of the boronic acid toward the Pd–halide complex by converting it into the respective organoborate. In addition, boric acid, an important reaction byproduct, affects the selectivity in the Suzuki reaction because its gradual formation in the reaction medium disturbs the acid–base equilibrium.

Ohmic heating as a new efficient process for organic synthesis in water

A new and efficient process for organic synthesis in aqueous media based on a direct ohmic heating reactor is described. Four representative organic transformations, a Diels–Alder cycloaddition, a nucleophilic substitution, an N-alkylation and a Suzuki cross-coupling reaction, were performed using this process. The results, when compared with those obtained under conventional external heating (oil bath) and microwave heating, showed that ohmic reactor allows faster and more uniform heating and an induced increase of dynamics/mobility of charged species leading in several cases to higher reaction yields and shorter reaction times.

Dimethyldioxirane Oxidation of (E,E)-Cinnamylideneacetophenones

The (E,E)-cinnamylideneacetophenones 1a−f were oxidised by isolated dimethyldioxirane (DMD, as acetone solution) at room temperature, giving diastereomeric mixtures of the α,β:γ,δ-diepoxides 3a−f when an excess of oxidant was used. α,β-Monoepoxides, found as minor components of the reaction, could be detected in only two cases (2c,d) when one equivalent of DMD was used. Dimethyldioxirane oxidation of (E,E)-2′-hydroxycinnamylideneacetophenones (4a−d) led to the formation of diastereomeric mixtures of the α,β:γ,δ-diepoxides 6a−d as well as to the γ,δ-monoepoxides 5a−d as minor products. The diepoxides 6a−d were transformed into the isolable coumaranone derivatives 7a−d during their chromatographic purification. All the compounds described have been fully characterised by NMR spectroscopy.

Ohmic Heating-Assisted Synthesis of 3-Arylquinolin-4(1H)-ones by a Reusable and Ligand-Free Suzuki–Miyaura Reaction in Water

Potential bioactive 3-arylquinolin-4(1H)-ones were synthesized under ohmic heating using an efficient, reusable, and ligand-free protocol developed for the Suzuki-Miyaura coupling of 1-substituted-3-iodoquinolin-4(1H)-ones with several boronic acids in water using Pd(OAc)2 as a catalyst and tetrabutylammonium bromide (TBAB) as the phase transfer catalyst. Good substrate generality, ease of execution, short reaction time, and practicability make this method exploitable for the generation of libraries of B ring-substituted 3-arylquinolin-4(1H)-ones. After a simple workup, the Pd/catalyst-H2O-TBAB system could be reused for at least seven cycles without significant loss of activity.

The structure of azines derived from C-formyl-1H-imidazoles in solution and in the solid state: Tautomerism, configurational and conformational studies

The structures of three azines derived from 2‐formylimidazole, 4(5)‐formylimidazole, and 4(5)‐formyl‐5(4)‐methylimidazole have been determined in solution and in the solid state. Density Functional Theory (DFT) Polarizable Continuum Model (PCM) calculations (geometries, energies, and chemical shifts), NMR [solution and cross polarization magic‐angle spinning (CPMAS)], and X‐ray crystallography [azine of 4(5)‐formylimidazole] have been used. The configuration around the central C = N bonds has been determined and some insights about prototropic tautomerism and conformation have been gained. Copyright

Ohmic heating assisted synthesis of coumarinyl porphyrin derivatives

Ohmic heating offers a very efficient way of performing organic reactions using water as solvent. An efficient access to new coumarinyl porphyrin derivatives bearing pyrano[3,2-c]coumarin motifs at the β-pyrrolic position of porphyrin macrocycles is disclosed by using this type of heating. The synthetic strategy involved a sequential Knoevenagel and hetero-Diels–Alder reaction between 2-vinyl-5,10,15,20-tetraphenylporphyrinatozinc(II) and α-methylenechromane derivatives generated in situ from 4-hydroxycoumarin and aromatic aldehydes in aqueous media. The results obtained under ohmic heating were compared with those obtained under conventional heating using water and also organic solvents.

Off-site impacts of wildfires on aquatic systems — Biomarker responses of the mosquitofish Gambusia holbrooki

The number of wildfires has markedly increased in Mediterranean Europe, including in Portugal. Wildfires are environmentally concerning, not only due to the loss of biodiversity and forest area, but also as a consequence of environmental contamination by specific compounds including metals and polycyclic aromatic compounds (PAHs). These contaminants, mostly bound to ashes, can reach downstream water bodies, namely through surface runoff, being ultimately dispersed by vast areas and contacting with aquatic biota. Being toxicologically noteworthy, the potential toxic outcomes of the input of such chemicals across the aquatic compartment must be characterized. In this context, the present study used a biomarker-based approach to find early-warning signals of toxicity triggered by the exposure of the mosquitofish, Gambusia holbrooki, to affected aqueous runoff and stream water samples collected from a forest burnt area. The chemical analysis revealed concerning levels of metals and polycyclic aromatic hydrocarbons in both runoff and stream water samples. Biological responses elicited by the collected samples showed the occurrence of pro-oxidative modifications, specifically driven by enzymatic forms involved in the metabolism of glutathione. Despite these effects, no further signs of involvement of metals and PAHs were elicited in terms of neurotoxicity. The overall set of data implicates chemicals resulting from wildfires in clear deleterious effects in exposed fish.

Synthesis, antibacterial and cytotoxic activities of new biflorin-based hydrazones and oximes.

Biflorin 1 is a biologically active quinone, isolated from Capraria biflora. Five new biflorin-based nitrogen derivatives were synthesized, of which two were mixtures of (E)- and (Z)- isomers: (Z)-2a, (Z)-2b, (Z)-3a, (Z)- and (E)-3b, (Z)- and (E)-3c. The antibacterial activity was investigated using the microdilution method for determining the minimum inhibitory concentration (MIC) against six bacterial strains. Tests have shown that these derivatives have potential against all bacterial strains. The cytotoxic activity was also evaluated against three strains of cancer cells, but none of the derivatives showed activity.

The structures of two aldazines: [1,1'-(1E,1'E)-hydrazine-1,2-diylidenebis(methan-1-yl-1-ylidene)dinaphthalen-2-ol] (Lumogen) and 2,2'-(1E,1'E)-hydrazine-1,2-diylidenebis(methan-1-yl-1-ylidene)diphenol (salicylaldazine) in the solid state and in solution.

A combination of NMR spectroscopy and theoretical methods Density functional theory including dispersion corrections (DFT‐D) was used to study the structures of Lumogen and salicylaldazine. In the solid state, Lumogen exists as the dihydroxy tautomer 1a (an azine, CN–NC) as was already known from an X‐ray determination. In a deuterated dimethyl sulfoxide solution, another tautomer is observed besides 1a; its structure corresponds to the hydroxy‐oxo tautomer 1b (a hydrazone, CN–NH–Csp2). In what concerns salicylaldazine, we have observed only the dihydroxy tautomer 2a. Copyright

Arylxanthones and arylacridones: a synthetic overview

Abstract Arylxanthones and arylacridones although not yet found in nature are becoming an important group of heterocyclic compounds due to their promising biological activities. Their central cores, xanthone and acridone, are recognized as interesting motifs for drug development mainly to be used in antitumour chemotherapy. The synthesis of this type of compounds is still scarce but several successful examples were recently published and a large variety of arylated xanthone and acridone derivatives were prepared. A systematic survey of the literature dedicated to their synthesis will be presented and discussed in this review.