Ana S. M. C. Rodrigues

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.

Effect of the Methylation and N-H Acidic Group on the Physicochemical Properties of Imidazolium-Based Ionic Liquids.

This work presents and highlights the differentiation of the physicochemical properties of the [C1Him][NTf2], [C2Him][NTf2], [(1)C1(2)C1Him][NTf2], and [(1)C4(2)C1(3)C1im][NTf2] that is related with the strong bulk interaction potential, which highlights the differentiation on the physicochemical arising from the presence of the acidic group (N-H) as well as the methylation in position 2, C(2), of the imidazolium ring. Densities, viscosities, refractive indices, and surface tensions in a wide range of temperatures, as well as isobaric heat capacities at 298.15 K, for this IL series are presented and discussed. It was found that the volumetric properties are barely affected by the geometric and structural isomerization, following a quite regular trend. A linear correlation between the glass transition temperature, Tg, and the alkyl chain size was found; however, ILs with the acidic N-H group present a significant higher Tg than the [(1)CN-1(3)C1im][NTf2] and [(1)CN(3)CNim][NTf2] series. It was found that the most viscous ILs, ([(1)C1Him][NTf2], [(1)C2Him][NTf2], and [(1)C1(2)C1Him][NTf2]) have an acidic N-H group in the imidazolium ring in agreement with the observed increase of energy barrier of flow. The methylation in position 2, C(2), as well as the N-H acidic group in the imidazolium ring contribute to a significant variation in the cation-anion interactions and their dynamics, which is reflected in their charge distribution and polarizability leading to a significant differentiation of the refractive indices, surface tension, and heat capacities. The observed differentiation of the physicochemical properties of the [(1)C1Him][NTf2], [(1)C2Him][NTf2], [(1)C1(2)C1Him][NTf2], and [(1)C4(2)C1(3)C1im][NTf2] are an indication of the stronger bulk interaction potential, which highlights the effect that arises from the presence of the acidic group (N-H) as well as the methylation in position 2 of the imidazolium ring.

Nanostructuration Effect on the Thermal Behavior of Ionic Liquids.

This work shows how the nanostructuration of ionic liquids (ILs) governs the glass and melting transitions of the bistriflimide imidazolium-based [Cn C1 im][NTf2 ] and [Cn Cn im][NTf2 ] series, which highlights the trend shift that occurs at the critical alkyl size (CAS) of n=6. An initial increase in the glass temperature (Tg ) with an increase in the alkyl side chain was observed due to the intensification of the dispersive interactions (van der Waals). Above the CAS, the -CH2 - increment has the same effect in both glass and liquid states, which leads to a plateau in the glass transition after nanostructuration. The melting temperature (Tm ) of the [Cn C1 im][NTf2 ] and [Cn Cn im][NTf2 ] series presents a V-shaped profile. For the short-alkyl ILs, the -CH2 - increment affects the electrostatic ion pair interactions, which leads to an increase in the conformational entropy. The -CH2 - increment disturbs the packing ability of the ILs and leads to a higher entropy value (ΔslSm○ ) and consequently a decrease in Tm . Above the CAS, the -CH2 - contribution to the melting temperature becomes more regular, as a consequence of the nanostructuration of the IL into polar and nonpolar domains. The dependence of the alkyl chain on the temperature, enthalpy, and entropy of melting in the ILs above the CAS is very similar to the one observed for the alkane series, which highlights the importance of the nonpolar alkyl domains on the ILs thermal behavior.

Effect of Confined Hindrance in Polyphenylbenzenes

A comprehensive thermodynamic study of the whole ortho-polyphenylbenzenes series from biphenyl (n = 1) to hexaphenylbenzene (n = 6) is presented. Combustion calorimetry and phase equilibria measurements for 1,2,3,4-tetraphenylbenzene (n = 4) and pentaphenylbenzene (n = 5) together with literature data were used to understand and quantify the constraint effect of ortho-substitution on the molecular energetics and phase stability of polyaromatic compounds. All of the derived thermodynamic properties (enthalpy of sublimation, entropy of sublimation, and gas phase molecular energetics) show a marked trend shift at n = 4 to 5, which is related to the change of the degree of molecular flexibility after 1,2,3,4-tetraphenylbenzene (n = 4). The greater intramolecular constraint in the more crowded members of the series (n = 5 and 6) leads to a significant change in the molecular properties and cohesive energy. The trend shift in the molecular properties is related with the decrease in molecular flexibility, which leads to lower molecular entropy and destabilization of the intramolecular interaction potential due to the increased hindrance in a confined molecular space.

Bevacizumab in the treatment of metastatic breast cancer: three case reports.

Case reports are presented for three patients with metastatic breast cancer who received first-line treatment with bevacizumab in combination with taxanes in clinical trials. Two patients showed peak reductions in lesion size of 49 and 70%, respectively. In one patient, subsequent treatment with bevacizumab in combination with capecitabine [Xeloda (after discontinuation of paclitaxel due to asthenia)] yielded peak reductions in target lesion size of 78%. One patient experienced a progression-free survival time of 16 months. In all three patients, bevacizumab was well tolerated and mostly displayed only mild toxicities.

2,4,5-Tris(biphenyl-2-yl)-1-bromo­benzene

In the title compound, C42H29Br, the dihedral angles between the central benzene ring and the three attached benzene rings are very similar, lying in the range 52.65 (6)–57.20 (7)°. Of the dihedral angles between the rings of the o-biphenyl substituents, two are similar [46.34 (7) and 47.35 (7)°], while the other differs significantly [64.17 (7)°]. In the crystal, molecules are linked into centrosymmetric dimers by two weak C—H⋯π interactions.

Comparison of the structure of (E)-2-(2-benzylidenehydrazinylidene)quinoxaline with those of its chloro- and bromobenzylidene analogues.

(E)-2-(2-Benzylidenehydrazinylidene)quinoxaline, C₁₅H₁₂N₄, crystallized with two molecules in the asymmetric unit. The structures of six halogen derivatives of this compound were also investigated: (E)-2-[2-(2-chlorobenzylidene)hydrazinylidene]quinoxaline, C₁₅H₁₁ClN₄; (E)-2-[2-(3-chlorobenzylidene)hydrazinylidene]quinoxaline, C₁₅H₁₁ClN₄; (E)-2-[2-(4-chlorobenzylidene)hydrazinylidene]quinoxaline, C₁₅H₁₁ClN₄; (E)-2-[2-(2-bromobenzylidene)hydrazinylidene]quinoxaline, C₁₅H₁₁BrN₄; (E)-2-[2-(3-bromobenzylidene)hydrazinylidene]quinoxaline, C₁₅H₁₁BrN₄; (E)-2-[2-(4-bromobenzylidene)hydrazinylidene]quinoxaline, C₁₅H₁₁BrN₄. The 3-Cl and 3-Br compounds are isomorphous, as are the 4-Cl and 4-Br compounds. In all of these compounds, it was found that the supramolecular structures are governed by similar predominant patterns, viz. strong intermolecular N-H...N(pyrazine) hydrogen bonds supplemented by weak C-H∙∙∙N(pyrazine) hydrogen-bond interactions in the 2- and 3-halo compounds and by C-H∙∙∙Cl/Br interactions in the 4-halo compounds. In all compounds, there are π-π stacking interactions.