Study of the Ternary Mixture of Methanol/Formamide/Acetonitrile via Solvatochromic Probes.

Following previous studies, the ternary mixture of methanol/formamide/acetonitrile (MeOH/Formamide/MeCN) was studied using the UV-Vis absorption spectra at 298.15 K with a set of five probes, 4-nitroaniline, 4-nitroanisole, 4-nitrophenol, N,N-dimethyl-4-nitroaniline and 2,6-diphenyl-4-(2,4,6-triphenyl-1-pyridinio)phenolate (Reichardt betaine dye), for a total of 22 mole ternary fractions. In addition, nine mole fractions of the underling binary mixtures, MeOH/Formamide and Formamide/MeCN were also tested. Spectroscopic results were used to model the preferential solvation order for each probe in the mixtures. The Kamlet-Taft solvatochromic solvent parameters, α, ß, and π*, were also computed through the use of the solvatochromic shifts of the five probe indicators. Moreover, discrepancies in the spectroscopic behavior of 4-nitrophenol in formamide-rich mixtures were observed and analyzed.

Hierarchical Zeolites Prepared Using a Surfactant-Mediated Strategy: ZSM-5 vs. Y as Catalysts for Friedel-Crafts Acylation Reaction.

Hierarchical ZSM5 and Y zeolites were prepared through a surfactant-mediated strategy with NH4OH changing the duration of the treatment and the amount of CTAB surfactant and taking as reference multiples of the critical micellar concentration (CMC). The materials were characterized using powder X-ray diffraction, N2 adsorption isotherms at -196 °C, and SEM and TEM microscopy. The catalytic performance was evaluated in Friedel-Crafts acylation of furan with acetic anhydride at 80 °C. The alkaline surfactant-mediated treatment had different effects on the two zeolites. For ZSM5, the CTAB molecular aggregates can hardly diffuse inside the medium-size pores, leading mainly to intercrystalline mesoporosity and increased external surface area, with no positive catalytic impact. On the other hand, for large-pore Y zeolite, the CTAB molecular aggregates can easily diffuse and promote the rearrangement of crystal units around micelles, causing the enlargement of the pores, i.e., intracrystalline porosity. The optimized Y-based sample, treated for 12 h with a CTAB amount 32 times the CMC, shows an increase in product yield and rate constant that was not observed when a higher amount of surfactant was added. The reuse of spent catalysts upon thermal treatment at 400 °C shows a regeneration efficiency around 90%, showing good potentialities for the modified catalysts.

Properties of the tert-butyl halide solvolysis transition states.

We have obtained properties (or descriptors) of the transition states in the solvolysis of tert-butyl chloride, bromide and iodide. We show that all three transition states, in both protic and in aprotic solvents, are highly dipolar and are strong hydrogen bond acids and strong hydrogen bond bases, except for the tert-butyl iodide transition state in aprotic solvents, which has a rather low hydrogen bond acidity. Thus, the transition states are stabilized by solvents that are hydrogen bond bases (nucleophiles) and are hydrogen bond acids (electrophiles). We show also that the partition of the transition states between water and solvents is aided by both nucleophilic and electrophilic solvents and conclude that the rate of solvolysis of the three halides is increased by both nucleophilic and electrophilic solvents.

Probing Substrate/Catalyst Effects Using QSPR Analysis on Friedel-Crafts Acylation Reactions over Hierarchical BEA Zeolites.

Attempts to optimize heterogeneous catalysis often lack quantitative comparative analysis. The use of kinetic modelling leads to rate (k) and relative sorption equilibrium constants (K), which can be further rationalized using Quantitative Structure-Property Relationships (QSPR) based on Multiple Linear Regressions (MLR). Friedel-Crafts acylation using commercial and hierarchical BEA zeolites as heterogeneous catalysts, acetic anhydride as the acylating agent, and a set of seven substrates with different sizes and chemical functionalities were herein studied. Catalytic results were correlated with the physicochemical properties of substrates and catalysts. From this analysis, a robust set of equations was obtained allowing inferences about the dominant factors governing the processes. Not entirely surprising, the rate and sorption equilibrium constants were found to be explained in part by common factors but of opposite signs: higher and stronger adsorption forces increase reaction rates, but they also make the zeolite active sites less accessible to new reactant molecules. The most relevant parameters are related to the substrates' molecular size, which can be associated with different reaction steps, namely accessibility to micropores, diffusion capacity, and polarizability of molecules. The relatively large set of substrates used here reinforces previous findings and brings further insights into the factors that hamper/speed up Friedel-Crafts reactions in heterogeneous media.

Design, synthesis and biological evaluation of novel isoniazid derivatives with potent antitubercular activity.

The disturbing emergence of multidrug-resistant strains of Mycobacterium tuberculosis (Mtb) has been driving the scientific community to urgently search for new and efficient antitubercular drugs. Despite the various drugs currently under evaluation, isoniazid is still the key and most effective component in all multi-therapeutic regimens recommended by the WHO. This paper describes the QSAR-oriented design, synthesis and in vitro antitubercular activity of several potent isoniazid derivatives (isonicotinoyl hydrazones and isonicotinoyl hydrazides) against H37Rv and two resistant Mtb strains. QSAR studies entailed RFs and ASNNs classification models, as well as MLR models. Strict validation procedures were used to guarantee the models' robustness and predictive ability. Lipophilicity was shown not to be relevant to explain the activity of these derivatives, whereas shorter N-N distances and lengthy substituents lead to more active compounds. Compounds 1, 2, 4, 5 and 6, showed measured activities against H37Rv higher than INH (i.e., MIC ≤ 0.28 µM), while compound 9 exhibited a six fold decrease in MIC against the katG (S315T) mutated strain, by comparison with INH (i.e., 6.9 vs. 43.8 µM). All compounds were ineffective against H37RvINH (ΔkatG), a strain with a full deletion of the katG gene, thus corroborating the importance of KatG in the activation of INH-based compounds. The most potent compounds were also shown not to be cytotoxic up to a concentration 500 times higher than MIC.

UV-Vis spectroscopic study of preferential solvation and intermolecular interactions in methanol/1-propanol/acetonitrile by means of solvatochromic probes.

Solvatochromic UV-Vis shifts of four indicators (4-nitroaniline, 4-nitroanisole, 4-nitrophenol and N,N-dimethyl-4-nitroaniline) have been measured at 298.15K in the ternary mixture methanol/1-propanol/acetonitrile (MeOH/1-PrOH/MeCN) in a total of 22 mole fractions, along with 18 additional mole fractions for each of the corresponding binary mixtures, MeOH/1-PrOH, 1-PrOH/MeCN and MeOH/MeCN. These values, combined with our previous experimental results for 2,6-diphenyl-4-(2,4,6-triphenylpyridinium-1-yl)phenolate (Reichardt's betaine dye) in the same mixtures, permitted the computation of the Kamlet-Taft solvent parameters, α, ß, and π(*). The rationalization of the spectroscopic behavior of each probe within each mixture's whole mole fraction range was achieved through the use of the Bosch and Rosés preferential solvation model. The applied model allowed the identification of synergistic behaviors in MeCN/alcohol mixtures and thus to infer the existence of solvent complexes in solution. Also, the addition of small amounts of MeCN to the binary mixtures was seen to cause a significant variation in π(*), whereas the addition of alcohol to MeCN mixtures always lead to a sudden change in α and ß. The behavior of these parameters in the ternary mixture was shown to be mainly determined by the contributions of the underlying binary mixtures.

The influence of carbon-carbon multiple bonds on the solvolyses of tertiary alkyl halides: A Grunwald-Winstein analysis.

The influence of carbon-carbon multiple bonds on the solvolyses of 3-chloro-3-methylbutyne (1), 2-chloro-2-phenylpropane (2), 2-bromo-2-methyl-1-phenylpropane (3), 4-chloro-4-methyl-2-pentyne (4) and 2-chloro-2-methylbutane (5) is critically evaluated through the extended Grunwald-Winstein equation. Substrates 1, 3 and 5 lead to correlations with unexpected negative sensitivity, h, to changes in the aromatic ring parameter, I. It is claimed that I is not a pure parameter, reflecting also some solvent nucleophilicity, N(OTs), character. In substrates 2 and 4 the possibility of rearside solvation is reduced due to steric hindrance and/or cation stabilization and the best found correlations involve only the solvent ionizing power, Y, and I.