Toxic Reagents Research Articles

In-Flow Generation of Thionyl Fluoride (SOF2) Enables the Rapid and Efficient Synthesis of Acyl Fluorides from Carboxylic Acids.

Herein, we report an approach for generating thionyl fluoride (SOF2) from the commodity chemicals thionyl chloride (SOCl2) and potassium fluoride (KF). The methodology relies on a microfluidic device that can efficiently produce and dose this toxic gaseous reagent under extremely mild and safe conditions. Subsequently, the in situ-generated thionyl fluoride is reacted with an array of structurally and electronically differing carboxylic acids, leading to the direct and efficient synthesis of highly sought-after acyl fluorides. Importantly, our investigation also highlights the inherent modularity of this flow-based platform. We demonstrate the adaptability of this approach by not only synthesizing acyl fluorides but also directly converting carboxylic acids into a diverse array of valuable compounds such as esters, thioesters, amides, and ketones. This versatility showcases the potential of this approach for a wide range of synthetic applications, underscoring its significance in the realm of chemical synthesis.

Fast and facile sonochemical fabrication of covalent organic frameworks in water for the adsorption of flavonoids: Adsorption behaviors and mechanisms

Solvothermal synthesis of covalent organic frameworks (COFs) typically requires high temperatures exceeding 120 °C, large amounts of toxic organic reagents, and reaction durations spanning 3–7 days. In contrast, a new COF (TFPPy-AD) was rapidly synthesized by the sonochemical method at room temperature within just 60 min, eliminating the need for toxic reagents. The characterization of the material showed that TFPPy-AD was successfully synthesized with notable features such as a large pore size, high crystallinity, and good thermal stability. Subsequent adsorption experiments highlighted the material's exceptional adsorption capacity and selectivity for flavonoids. The adsorption mechanism of flavonoids onto TFPPy-AD likely involves a combination of sieve interactions, hydrogen bonding interactions, hydrophobic interactions, and π-π interactions. This sonochemically synthesized COF exhibits promising attributes including high adsorption capacity, selectivity, and rapid adsorption rate for flavonoids, suggesting potential applications in the separation and purification of flavonoids in natural medicines.

Continuous preparation and reaction of nonaflyl azide (NfN3) for the synthesis of organic azides and 1,2,3-triazoles

Organic azides are widely used in organic synthesis. Continuous flow processing can be used to bypass their isolation, and can therefore be useful in mitigating the hazards associated with these potentially toxic and explosive reagents. Nonaflyl azide has been reported as an effective, bench-stable, and relatively safe diazo transfer reagent that can be useful in the preparation of azides from amines and so avoid the use of alkyl halides. Here we demonstrate the synthesis and purification of nonaflyl azide in continuous flow with isolation of the neat, pure reagent by membrane filtration. The neat reagent was used in the preparation of organic azides from primary amines, and then applied to the synthesis of triazoles. A variety of triazoles, including the antiseizure drug Rufinamide, were prepared from primary amines and alkynes via the CuAAC click reaction in a semi-batch parallel array without isolation of alkyl azide intermediates. A telescoped two-stage continuous flow process was also designed and demonstrated to form triazoles via the same CuAAC reaction, which avoids the handling of the intermediate reactive azides.

Development of In-Water Scalable Process for the Preparation of [2-(3-Bromo-2-methylphenyl)-7-chloro-1,3-benzoxazol-5-yl]methanol, a Key Intermediate in the Synthesis of Potent PD-1/PD-L1 Inhibitors

AbstractWe propose a synthetic process for the preparation of a benzoxazole building block for a programmed death-ligand 1 inhibitor that is a candidate currently under clinical investigation for cancer treatment. Our research focused on searching for mild, scalable, and ecofriendly conditions for the synthesis of benzoxazoles. To reduce the use of toxic reagents or solvents and to minimize the production of organic wastes, the cyclization reaction was performed in an aqueous micellar medium. This in-water benzoxazole synthesis gave comparable yields to previously reported processes, and was applied to a broad range of benzoxazoles with various substitution patterns, showcasing its effectiveness in ecofriendly benzoxazole cyclization reactions.

An eco-friendly approach for analysing sugars, minerals, and colour in brown sugar using digital image processing and machine learning

Brown sugar is a natural sweetener obtained by thermal processing, with interesting nutritional characteristics. However, it has significant sensory variability, which directly affects product quality and consumer choice. Therefore, developing rapid methods for its quality control is desirable. This work proposes a fast, environmentally friendly, and accurate method for the simultaneous analysis of sucrose, reducing sugars, minerals and ICUMSA colour in brown sugar, using an innovative strategy that combines digital image processing acquired by smartphone cell with machine learning. Data extracted from the digital images, as well as experimentally determined contents of the physicochemical characteristics and elemental profile were the variables adopted for building predictive regression models by applying the kNN algorithm. The models achieved the highest predictive capacity for the Ca, ICUMSA colour, Fe and Zn, with coefficients of determination (R2) ≥ 92.33 %. Lower R2 values were observed for sucrose (81.16 %), reducing sugars (85.67 %), Mn (83.36 %) and Mg (86.97 %). Low data dispersion was found for all the predictive models generated (RMSE < 0.235). The AGREE Metric assessed the green profile and determined that the proposed approach is superior in relation to conventional methods because it avoids the use of solvents and toxic reagents, consumes minimal energy, produces no toxic waste, and is safer for analysts. The combination of digital image processing (DIP) and the kNN algorithm provides a fast, non-invasive and sustainable analytical approach. It streamlines and improves quality control of brown sugar, enabling the production of sweeteners that meet consumer demands and industry standards.

Pozyskiwanie złota ze słowackiego koncentratu przy użyciu innowacyjnej metody

The complicated processing of concentrates with low gold content and the long-time use of non-ecological methods was the motion for finding a more efficient process for this noble metal obtaining. From this point of view, this research was focused on obtaining of nano gold from the concentrate White Hill (Detva, Slovakia) using mechanical activation and mechano-biological activation in a molecular hydrogen solution. Gold in this complex concentrate occurs physically enclosed in the intercrystalline space of minerals and is also isomorphic and fills defects in their structure. The exclusion of gold from such complex mineral matrixes of the concentrate can be achieved using a mechano-biological process. This innovative method for obtaining of nano gold with the application of a molecular hydrogen solution is an advantageous alternative to the non-environmental reagents used. Compared to the most used worldwide toxic cyanide reagent, a solution with molecular hydrogen represents a low-cost and above all completely harmless reagent with very good kinetics. Mechanical processes use high-energy milling, which has an effect on the more intensive formation of surface and bulk defects in solid substances. The main advantage of mechanical processes is a smaller number of technological operations, a shorter time required to obtain the desired product at favorable environmental temperatures, and also the formation of nanostructures. The use of a biological process with the application of limnetic algae showed that algae with siliceous structures make it possible to obtain gold from the White Hill concentrate with nanoscale size. Limnetic algae (diatoms, golden algae) are part of aquatic ecosystems and create the largest matter of biomass from all plants on the Earth. The mechano-biological process is a method that enabled to obtain of gold nanoparticles with an average size of 100 nm from the Slovak gold-bearing concentrate from the White Hill deposit (BV-1). Mechanical activation of this concentrate and siliceous shells of the specified limnetic algae (Dinobryon, Surirella) in a molecular hydrogen solution caused changes in the physical-chemical properties of gold minerals as well as in the constituents of algae minerals. These structural changes had a decisive influence on the exclusion of gold nanoparticles into the molecular hydrogen solution under the defined reaction conditions. The gold nanoparticles were subsequently fixed in the cellular matrix of mechanically activated algae shells. The explanation of this phenomenon was the action of biomolecules, which the algae cells secreted in the course of reactions with metal ions present in the molecular hydrogen solution. Gold nanoparticles from the investigated concentrate were obtained by a new mechano-biological procedure already for four hours. In the case of mechanical activation of the concentrate, but without activation of the used algae, gold nanoparticles were excluded after sixteen hours. It follows from this knowledge that the application of an absolutely ecologically harmless aqueous solution enriched by molecular hydrogen and the use of limnetic algae confirmed the suitability of the innovative method for obtaining of nano gold from the concentrate. From the achieved research results significantly more effective kinetics is evident in the case of activated algae. Nanoparticles of gold obtained by the mentioned procedure can have important practical utilization, such as accelerating of the decomposition of dangerous substances or neutralizing pollutants in contaminated water, soil, and air. Simultaneously, obtaining of gold nanoparticles would also be beneficial for removing algae from the aquatic environment, where they are very dangerous for all living organisms.

Advances in the synthesis of cytidine-5'-diphosphate choline

Cytidine-5'-diphosphate choline (CDP-choline) plays a crucial role in the formation of the phospholipid bilamolecular layer in cell membranes and the stabilization of the neurotransmitter system, acting as a precursor to phosphatidylcholine and acetylcholine. CDP-choline has been found effective in treating functional and consciousness disorders resulting from brain injury, Parkinson's disease, depression and glaucoma, and other conditions. As such, CDP-choline is widely utilized in clinical medicine and health care products. The conventional chemical synthesis process of CDP-choline is gradually being replaced by biosynthesis due to the expensive and toxic reagents involved, the production of various by-products, and the high cost of industrial production. Biosynthesis of CDP-choline offers two strategies: microbial fermentation and biocatalysis. Microbial fermentation utilizes inexpensive raw materials but results in a relatively low conversion rate and requires a complex separation and purification process. Biocatalysis, on the other hand, involves two stages: the growth of a living "catalyst" and the conversion of the substrate. Although the synthetic process in biocatalysis is more complex, it offers a higher conversion ratio, and the downstream processing technique for extraction is relatively less costly. Consequently, biocatalysis is currently the primary strategy for the industrial production of CDP-choline. This review aims to summarize the progress made in both chemical synthesis and biosynthesis of CDP-choline, with particular focus on the metabolic pathway and the synthetic processes involved in biocatalysis, in order to provide insights for the industrial production of CDP-choline.

Hydrophilization and Functionalization of Fullerene C60 with Maleic Acid Copolymers by Forming a Non-Covalent Complex.

In this study, we report an easy approach for the production of aqueous dispersions of C60 fullerene with good stability. Maleic acid copolymers, poly(styrene-alt-maleic acid) (SM), poly(N-vinyl-2-pyrrolidone-alt-maleic acid) (VM) and poly(ethylene-alt-maleic acid) (EM) were used to stabilize C60 fullerene molecules in an aqueous environment by forming non-covalent complexes. Polymer conjugates were prepared by mixing a solution of fullerene in N-methylpyrrolidone (NMP) with an aqueous solution of the copolymer, followed by exhaustive dialysis against water. The molar ratios of maleic acid residues in the copolymer and C60 were 5/1 for SM and VM and 10/1 for EM. The volume ratio of NMP and water used was 1:1.2-1.6. Water-soluble complexes (composites) dried lyophilically retained solubility in NMP and water but were practically insoluble in non-polar solvents. The optical and physical properties of the preparations were characterized by UV-Vis spectroscopy, FTIR, DLS, TGA and XPS. The average diameter of the composites in water was 120-200 nm, and the ξ-potential ranged from -16 to -20 mV. The bactericidal properties of the obtained nanostructures were studied. Toxic reagents and time-consuming procedures were not used in the preparation of water-soluble C60 nanocomposites stabilized by the proposed copolymers.

Catalytic Hydroxyethylation of Phenols with Renewable Ethylene Glycol Diester as an Alternative to Ethylene Oxide

AbstractPolyol esters are abundant bio‐based resources. Integration of polyol esters into the production chain of fine chemicals would reduce carbon emissions and improve the sustainability of the chemical industry. An efficient synthetic route to phenoxyethanols was developed through catalytic hydroxyethylation of phenols with ethylene glycol diacetate as the reagent. This method showed the potential of ethylene glycol diester as a safe and sustainable substitute for ethylene oxide, a useful but toxic reagent. A variety of phenoxyethanol esters were produced in high yield under simple catalytic conditions. Mechanistic studies revealed that the reaction underwent a neighboring group participation process.

Hydrothiolation of Triisopropylsilyl Acetylene Sulfur Pentafluoride - Charting the Chemical Space of β-SF5 Vinyl Sulfides.

Recently, we suggested liquid and high-boiling TIPS-CC-SF5 (TASP) as a versatile reagent to access so far elusive SF5-containing building blocks by less specialized laboratories under bench-top conditions. The synthesis of non-aromatic SF5 building blocks generally requires on-site fluorination or pentafluorosulfanylation steps employing toxic and/or gaseous reagents. Herein, we underline the versatility of this reagent by reporting a benign bench-top protocol for the synthesis of Z-configured β-pentafluorosulfanylated vinyl sulfides in good to excellent yields (up to 99 %) with exclusive (Z)-diasteroselectivity and broad functional group tolerance. This method exploits an in-situ protodesilylation-hydrothiolation sequence. This so far uncharted class of compounds was characterized by means of NMR-spectroscopy as well as SC-XRD. Furthermore, we suggest the reaction to proceed via a kinetically controlled closed-shell reaction pathway, corroborated by in-silico experiments.

Electrochemical-induced direct approach to methylthiolated pyrazoles via a four-component one-pot strategy

Herein, a multicomponent electrochemical protocol for direct access to methylthiolated pyrazoles using potassium thiocyanate (KSCN) as sulfur source has been developed, where the methanol acts as both the solvent and the methylation reagent. This electrosynthesis strategy provides an eco-friendly and sustainable way to access methylthiolated pyrazoles by avoiding expensive metal catalysts and highly toxic sulfur reagent. Mechanism studies revealed that the key CH methylthiolation reaction proceeded via a radical pathway.

Recent Advances in Ball-Milled Materials and Their Applications for Adsorptive Removal of Aqueous Pollutants

Ball milling, as a cost-effective and eco-friendly approach, has been popular in materials synthesis to solve problems involving toxic reagents, high temperatures, or high pressure, which has the potential for large-scale production. However, there are few reviews specifically concentrating on the latest progress in materials characteristics before and after ball milling as well as the adsorptive application for aqueous pollutants. Hence, this paper summarized the principle and classification of ball milling and reviewed the advances of mechanochemical materials in categories as well as their adsorption performance of organic and inorganic pollutants. Ball milling has the capacity to change materials’ crystal structure, specific surface areas, pore volumes, and particle sizes and even promote grafting reactions to obtain functional groups to surfaces. This improved the adsorption amount, changed the equilibrium time, and strengthened the adsorption force for contaminants. Most studies showed that the Langmuir model and pseudo-second-order model fitted experimental data well. The regeneration methods include ball milling and thermal and solvent methods. The potential future developments in this field were also proposed. This work tries to review the latest advances in ball-milled materials and their application for pollutant adsorption and provides a comprehensive understanding of the physicochemical properties of materials before and after ball milling, as well as their effects on pollutants’ adsorption behavior. This is conducive to laying a foundation for further research on water decontamination by ball-milled materials.

Green Approach Toward Triazole Forming Reactions for Developing Anticancer Drugs.

Compounds containing triazole have many significant applications in the dye and ink industry, corrosion inhibitors, polymers, and pharmaceutical industries. These compounds possess many antimicrobial, antioxidant, anticancer, antiviral, anti-HIV, antitubercular, and anticancer activities. Several synthetic methods have been reported for reducing time, minimizing synthetic steps, and utilizing less hazardous and toxic solvents and reagents to improve the yield of triazoles and their analogues synthesis. Among the improvement in methods, green approaches towards triazole forming biologically active compounds, especially anticancer compounds, would be very important for pharmaceutical industries as well as global research community. In this article, we have reviewed the last five years of green chemistry approaches on click reaction between alkyl azide and alkynes to install 1,2,3-triazole moiety in natural products and synthetic drug-like molecules, such as in colchicine, flavanone cardanol, bisphosphonates, thiabendazoles, piperazine, prostanoid, flavonoid, quinoxalines, C-azanucleoside, dibenzylamine, and aryl-azotriazole. The cytotoxicity of triazole hybrid analogues was evaluated against a panel of cancer cell lines, including multidrug-resistant cell lines.

Advanced valorisation for cork wastewater

The cork manufacturing process generates cork boiling wastewater, characterized by high COD and phenolic compounds content. The main aim of this study is the advanced valorization of these spills through a green and efficient process with two main stages. Firstly, most of the organic matter was removed by an optimal design of a precipitation with calcium. The resulting depuration rates were in the ranges 37–53 % for COD and 70–87 % for TPC. Secondly, the precipitates generated were subjected to a biodigestion process with production of methane (up to 234 L CH4·kg VS−1) and fertilizers. In conclusion, good recovery of interesting by-products and a good yield of depuration were achieved with the technology proposed, avoiding the use of toxic reagents and demonstrating the potential of concentrate precipitates from CBWs as substrates for biodigestion.

Development of Ti3C2Tx‐based novel immunosensor for cancer biomarker detection

In this study, an ultrasensitive label‐free electrochemical immunosensor based on Ti3C2Tx (Mxene) with a 2D‐layered morphology has been proposed for the detection of EpCAM antigen. A hydrothermal method is employed for the synthesis of Ti3C2Tx by using a less toxic exfoliating reagent, NaBF4. The bioelectrode, BSA/anti‐EpCAM/Ti3C2Tx@ITO, has been fabricated by electrophoretic deposition of Ti3C2Tx onto the ITO electrode, followed by an immobilization of EpCAM antibody. Electrochemical response studies reveal that the immunosensor shows a high sensitivity of 29.22 μA fg−1 ml cm−2 and a wide linear range from 0.1 fg/ml to 100 ng/ml, for EpCAM antigen detection. Further, the good stability of this fabricated immunosensor is an additional advantage for EpCAM antigen detection in serum samples.

Hyperspectral Data for Early Identification and Classification of Potassium Deficiency in Soybean Plants (Glycine max (L.) Merrill)

Identifying potassium (K+) deficiency in plants has traditionally been a difficult and expensive process. Traditional methods involve inspecting leaves for symptoms and conducting a laboratory analysis. These methods are not only time-consuming but also use toxic reagents. Additionally, the analysis is performed during the reproductive stage of growth, which does not allow enough time for corrective fertilization. Moreover, soybean growers do not have other tools to analyze the nutrition status during the earlier stages of development. Thus, this study proposes a quick approach for monitoring K+ in soybean crops using hyperspectral data through principal component analysis (PCA) and linear discriminant analysis (LDA) with a wavelength selection algorithm. The experiment was carried out at the Brazilian National Soybean Research Center in the 2017–2018, 2018–2019, and 2019–2020 soybean crop seasons, at the stages of development V4–V5, R1–R2, R3–R4, and R5.1–R5.3. Three treatments were evaluated that varied in K+ availability: severe potassium deficiency (SPD), moderate potassium deficiency (MPD), and an adequate supply of potassium (ASP). Spectral data were collected using an ASD Fieldspec 3 Jr. hyperspectral sensor. The results showed a variation in the leaf spectral signature based on the K+ availability, with SPD having higher reflectance in the visible region due to a lower concentration of pigments. PCA explained 100% of the variance across all stages and seasons, making it possible to distinguish SPD at an early development stage. LDA showed over 70% and 59% classification accuracies for discriminating a K+ deficiency in the simulation and validation stages. This study demonstrates the potential of the method as a rapid nondestructive and accurate tool for identifying K+ deficiency in soybean leaves.

Visible‐Light Mediated Ugi‐Type Reaction for the Synthesis of 3,3‐Disubstituted Phthalides

AbstractThe synthesis of diverse phthalides containing quaternary carbon centers remains poorly exploited, requiring stepwise reactions with toxic reagents under high temperatures. Herein, we describe a visible‐light promoted, photo‐ and metal‐catalyst‐free protocol for the modular synthesis of 3,3‐disubstituted phthalides with water as the sole by‐product. This process featured an open‐flask operation of a three‐component reaction involving an isocoumarin as the self‐photosensitizer for aerobic ring contracting rearrangements, allowing the convenient preparation of 3‐(1′‐indolyl)‐phthalides in moderate to good yields. The mechanistic investigations suggested that singlet oxygen (1O2) was generated through an energy‐transfer pathway.

Design and realization of versatile durable fluorine-free anti-corrosive coating with robust superhydrophobicity

Bio-inspired superhydrophobic coatings are of increasing interest in marine corrosion protection due to their superior barrier and shielding effects. However, some difficult problems like weak mechanical strength, the use of costly and toxic reagents, and intricate preparation processes have long hindered the practical application of the superhydrophobic coatings. Herein, a durable, self-cleaning and anti-corrosion superhydrophobic coating based on epoxy resin matrix was successfully fabricated, avoiding the use of fluorine materials. The prepared coating possessed excellent superhydrophobicity and was applicable to a variety of substrates, which was ascribed to the effect of modified kaolin particles on lowering surface energy. Through SEM and LSCM, the superhydrophobic coatings manifested the morphology feature of "hills+mountain", which could store air to reduce solid-liquid contact. The prepared coating had been proven to have greater impedance modulus and charge transfer resistance by EIS test, and displayed outstanding durability in salt spray environment compared with pure epoxy coating. In addition, the sandpaper abrasion, standard cross-cut tape and self-cleaning tests indicated that the superhydrophobic coatings satisfied robust mechanical stability and excellent resistance to contaminants, laying the foundation for the application of superhydrophobic coating in practical environment.

Sustainable and efficient oil-water separation using bio tin oxide-based superhydrophobic membrane

IntroductionSuperhydrophobic materials are considered an ideal method for oil-water separation. However, existing oil-water separation methods have the problem of manufacturing complex and toxic chemical reagents. To address the limitation, we proposed a novel approach to sustainable and efficient oil-water separation using a superhydrophobic membrane based on the Bio Tin oxide nanoparticles (Bio-SnO2 NPs).MethodsThe study involves synthesizing Bio-SnO2 NPs from the sunflower leaf extract which was natural and non-toxic and modifying textile fabric with a superhydrophobic coating (S.T.F.). Characterization techniques including SEM, FTIR, and BET analysis are employed to assess the structural and textural properties of the modified membrane.Results and DiscussionThe textile fabric was modified with a superhydrophobic coating (S.T.F.), demonstrating enhanced wettability, oil absorption capacity, and oil-water separation performance. The Bio-SnO2 NPs exhibited crystalline structures with a length of 90 nm and a diameter of 20 nm, as confirmed by SEM analysis. FTIR results revealed characteristic peaks at 3410 cm-1 and 642 cm-1, indicating the presence of hydroxyl group and Sn-O bonds confirming the successful synthesis of Bio-SnO2 NPs. BET analysis showed a substantial specific surface area of 413 m2/g and a pore volume of 0.19 cm3/g, emphasizing the textural properties. The FTIR and SEM techniques were used to study the characteristics of the textile fabric before and after modification with the superhydrophobic coat. The S.T.F. exhibited remarkable superhydrophobicity with a water contact angle of 152° and a water sliding angle of 4°. Absorption capacities for coconut oil, diesel, and hexane were found to be 70.4 g/g, 63.5 g/g, and 49.6 g/g, respectively, with excellent cyclic stability. Separation efficiency for hexane, diesel, and coconut oil was found to be 99.5, 97.1%, and 96.3%, respectively, with excellent cyclic stability. Mechanical stability test revealed superhydrophobicity retention even after an abrasion length of 200 mm. The chemical stability test indicated that the superhydrophobicity was maintained in the pH range of 3-11. Moreover, the flux for hexane, diesel, and coconut oil was 9400 L m−2 h−1, 8800 L m−2 h−1, and 8100 L m−2 h−1, respectively, highlighting the membrane’s efficient oil-water separation capabilities. These results collectively position the developed S.T.F. as a promising and sustainable solution for diverse oil-water separation applications.

Transfer learning improves predictions in lignin content of Chinese fir based on Raman spectra

Lignin in biomass plays significant role in substitution of synthetic polymer and reduction of energy expenditure, and the lignin content was usually determined by wet chemical methods. However, the methods' heavy workload, low efficiency, huge consumption of chemicals and use of toxic reagents render them unsuitable for sustainable development and environmental protection. Chinese fir, a prevalent angiosperm tree, holds immense importance for various industries. Since our previous work found that Raman spectroscopy could accurately predict the lignin content in poplar, we propose that the lignin content of Chinese fir can be estimated by similar strategy. The results suggested that the peak at 2895 cm−1 is the optimal choice of internal standard peak and algorithm of XGBoost demonstrates the highest accuracy among all algorithms. Furthermore, transfer learning was successfully introduced to enhance the accuracy and robustness of the model. Ultimately, we report that a machine learning algorithm, combining transfer learning with XGBoost or LightGBM, offers an accurate, high-efficiency and environmental friendly method for predicting the lignin content of Chinese fir using Raman spectra.