Sulfur- and Amine- Promoted Multielectron Autoredox Transformation of Nitromethane: Multicomponent Access to Thiourea Derivatives.

Thiourea derivatives are in-demand motifs in organic synthesis, medicinal chemistry and material science, yet redox methods for the synthesis that start from safe, simple, inexpensive and readily available feedstocks are scarce. In this article, we disclose the synthesis of these motifs using elemental sulfur and nitromethane as the starting materials. The method harnesses the multi-electron auto-redox property of nitromethane in the presence of sulfur and amines, delivering thiourea products without any added oxidant or reductant. Extension of this reaction to cyclizable amines and/or higher homologues of nitromethane led to a wide range of nitrogen heterocycles and thioamides. Operationally simple, the reactions are scalable, tolerate a wide range of functional groups, and can be employed for the direct functionalization of natural products. Mechanistically, the nitro group was found to act as an oxidant leaving group, being reduced to ammonia whereas sulfur, along with the role of a sulfur building block for the thiocarbonyl group, behaved as a complementary reductant, being oxidized to sulfate.

Sodium sulfide-promoted regiodefined redox condensation of o-nitroanilines with aryl ketones to benzo[a]phenazines and quinoxalines.

Inexpensive sodium sulfide trihydrate was found to promote unprecedented 6e-regio-predefined redox condensation of o-nitroanilines with α-tetralones to benzo[a]phenazines. The method was also successfully extended to acetophenones and higher homologs as reducing partners to provide 2-phenylquinoxalines. Compared to traditional approaches toward benzo[a]phenazine and quinoxaline cores starting with o-phenylenediamines, the present strategy could afford these heterocycles with well-defined regiochemistry based on the structure of starting o-nitroanilines.

Fe/S-Catalyzed synthesis of 2-benzoylbenzoxazoles and 2-quinolylbenzoxazoles via redox condensation of o-nitrophenols with acetophenones and methylquinolines.

An Fe/S catalyst generated in situ from FeCl2·4H2O and elemental sulfur S8 in the presence of a tertiary amine as a base was found to catalyze efficiently a 6e- redox condensation of o-nitrophenols with acetophenones and methylquinolines. The condensed products 2-benzoylbenzoxazoles and 2-quinolylbenzoxazoles were obtained in reasonable yields with water as the only byproduct at a temperature as low as 80 °C.

Design, Synthesis and Biological Activities of New Pyrazole Derivatives Possessing Both Coxib and Combretastatins Pharmacophores.

In our efforts to discover novel multi-target agents having better antitumor activities than celecoxib, 21 new aryl-substituted pyrazole derivatives possessing cis-diphenylethylene scaffold were mostly synthesized by a one-pot approach to ethyl 1,4,5-triaryl-1H-pyrazole-3-carboxylates via an improved Claisen condensation - Knorr reaction sequence. The cytotoxic effects of these compounds against three human cancer cell lines HT-29, Hep-G2, MCF-7 as well as their inhibition of NO production were studied. Results showed that incorporation of the important pharmacophoric groups of two original molecules celecoxib and combretastatin A-4 in a single molecule plays an important role in determining a better biological activities of the new coxib-hybrided compounds.

Synthesis and antiproliferativeactivity of new vinca alkaloids containing an α,ß-unsaturated aromatic side chain.

A new series of vinca-alkaloids derivatives containing various α,ß-unsaturated aromatic side chains was synthesized. Four new vinca-alkaloids derivatives showed selective cytotoxicities against KB tumor cell lines with IC50 value below 0.1 µM, thus comparable with vinblastine.

A multimodal analytical approach is important in accurately assessing terpene composition in edible essential oils.

Terpenes in essential oils (EOs) have recently received significant attention due to their potential to improve brain and whole-body health. A deeper understanding of the terpene composition of edible EOs is important for fully exploring their possible applications. In our study, we employed a comprehensive study using four different methods to analyze EO samples, including GC-MS with solid phase microextraction (SPME), liquid injection (LI), derivatization to trimethylsilyl ethers (TMSE), and LC-MS. Our findings revealed that relying on a single analytical method may be insufficient for detecting all terpenes in EOs. Despite identifying a total of 156 terpenes in the samples, only 58 were detectable across all 4 methods. To obtain a more accurate terpene profile of EOs, we advocate for the combined use of LI-GC and TMSE-GC. The terpenes detected by these two methods are complementary, enabling the detection of all terpenes with high VIP in the samples.

Sulfur-Promoted Access to 3-Arylquinoxalin-2-ones by Oxidative Coupling of o-Phenylenediamines with Arylacetates.

We disclose the synthesis of 3-arylquinoxalin-2-ones from o-phenylenediamines and readily available arylacetates. The method harnesses the selective oxidative property of elemental sulfur in the presence of amine base catalyst and DMSO. The reactions are operationally simple and tolerate a wide range of functional groups.

Fe/S-Catalyzed Redox Condensation of o-Nitrophenols with Isothiocyanates to 2-Aminobenzoxazoles.

As frequently encountered byproducts of isocyanate chemistry, hydrogen sulfide and related sulfur containing compounds should be treated in a safe way to lower their adverse health and environmental effects, especially in large scale syntheses. As a proof of concept, we report herein an example of in situ recycling of sulfur byproduct to reductant in the synthesis of bioactive 2-aminobenzoxazoles 3. Using an Fe/S catalytic system, this heterocyclic scaffold could be obtained from o-nitrophenols 1 with isothiocyates 2 via direct redox condensation consisting of reduction of the nitro group of 1 by the sulfur moiety of 2.

Solvents govern rheology and jamming of polymeric bead suspensions.

Despite their apparent simplicity, suspensions of hard spheres in a Newtonian fluid show complex non-Newtonian behaviors and remain poorly understood. Recent works have pointed out the crucial role of interparticle contact forces in these behaviors. Here, we show that the same (polystyrene) particles, when immersed in different Newtonian solvents, show different behaviors at both the microscopic and macroscopic scales. Thanks to interparticle force measurements in each solvent together with rheological measurements, we show how the fine details of the pairwise particle interactions impact the macroscopic behavior. The rheological properties (shear thinning, shear thickening, jamming solid fraction value) of the suspensions, made up of same particles, are shown to depend on the nature of the solvent. Here, we highlight several mechanisms at the particle scale: the swelling of polymeric particles in an organic solvent, the role of colloidal repulsive forces and inertia for particles in a water solution, and the variation of the friction coefficient as a function of the load for particles immersed in silicone oils. Our study provides new quantitative data to test micromechanical models and simulations. It questions the interpretation of previous experimental works. Finally, it shows the need to systematically characterize the interparticle normal and tangential forces when studying a given suspension of hard spheres in a Newtonian fluid.

Density waves in shear-thickening suspensions.

Shear thickening corresponds to an increase of the viscosity as a function of the shear rate. It is observed in many concentrated suspensions in nature and industry: water or oil saturated sediments, crystal-bearing magma, fresh concrete, silica suspensions, and cornstarch mixtures. Here, we reveal how shear-thickening suspensions flow, shedding light onto as yet non-understood complex dynamics reported in the literature. When shear thickening is important, we show the existence of density fluctuations that appear as periodic waves moving in the direction of flow and breaking azimuthal symmetry. They come with strong normal stress fluctuations of the same periodicity. The flow includes small areas of normal stresses of the order of tens of kilopascals and areas of normal stresses of the order of hundreds of pascals. These stress inhomogeneities could play an important role in the damage caused by thickening fluids in the industry.

Strategy for Contiguous Tetramination of Cyclohexanones with o-Phenylenediamines with Elemental Sulfur and DMSO.

The S8/DMSO combination was found to be an excellent oxidizing agent for ipso,α,ß,γ-tetramination of cyclohexanones with two molecules of o-phenylenediamines in the presence of TFA as a catalyst. The strategy could be applied to pyrido cyclohexanes as a direct method to extend the fused heteroaromatic system.

Abundance and prevalence of Aedes aegypti immatures and relationships with household water storage in rural areas in southern Viet Nam.

Since 2000, the Government of Viet Nam has committed to provide rural communities with increased access to safe water through a variety of household water supply schemes (wells, ferrocement tanks and jars) and piped water schemes. One possible, unintended consequence of these schemes is the concomitant increase in water containers that may serve as habitats for dengue mosquito immatures, principally Aedes aegypti. To assess these possible impacts we undertook detailed household surveys of Ae. aegypti immatures, water storage containers and various socioeconomic factors in three rural communes in southern Viet Nam. Positive relationships between the numbers of household water storage containers and the prevalence and abundance of Ae. aegypti immatures were found. Overall, water storage containers accounted for 92-97% and 93-96% of the standing crops of III/IV instars and pupae, respectively. Interestingly, households with higher socioeconomic levels had significantly higher numbers of water storage containers and therefore greater risk of Ae. aegypti infestation. Even after provision of piped water to houses, householders continued to store water in containers and there was no observed decrease in water storage container abundance in these houses, compared to those that relied entirely on stored water. These findings highlight the householders' concerns about the limited availability of water and their strong behavoural patterns associated with storage of water. We conclude that household water storage container availability is a major risk factor for infestation with Ae. aegypti immatures, and that recent investment in rural water supply infrastructure are unlikely to mitigate this risk, at least in the short term.

Reverse remodeling with resynchronization in an asymptomatic patient with dilated hypokinetic cardiomyopathy.

Cardiac resynchronization therapy (CRT) is a validated treatment for selected heart failure patients who remain highly symptomatic despite optimal drug treatment. Yet there is currently no indication for CRT in patients with few or no symptoms. We report a spectacular "reverse remodeling" effect after CRT in an asymptomatic patient with hypokinetic dilated myocardiopathy who needed pacing for atrio-ventricular conduction disorder. CRT was chosen to prevent deterioration of left ventricular function by conventional right apical pacing. Thus, CRT could be indicated in patients with hypokinetic dilated myocardiopathy before the appearance of symptoms.