Journal of Flow Chemistry最新文献

The employment of acetylene-derived alkenyl iodides facilitates the integration of olefinic moieties into intricate molecular structures. Their synthesis is often related to catalytic gas-liquid process where traditional batch methods suffer from inefficient mass transfer upon scaling, thus limiting yields of iodoolefins production. In this study, we develop microfluidic synthesis of vinyl iodide and (E,E)-1,4-diiodo-1,3-butadiene from acetylene using Pt^IV iodo complexes as a catalyst in aqueous solutions. Segmented Taylor flow regime was applied to increase interfacial surface area and subsequent gas-liquid separation enables online mass-spectroscopic conversion monitoring. We varied reaction parameters to study temperature dependence of the conversion as well as influence of gas and liquid flow rates. The optimal conditions were derived from Bayesian approach and promoted better mass transfer and, thereby, higher acetylene conversion. The methodology can be readily extended to the synthesis of other small organic iodides.

Continuous solvothermal syntheses of carbon-based nanomaterials (CBNs) provide an efficient route to generate optically active substances compared to batchwise synthesis. In this study, technical process control and in-line analytical data acquisition was applied. Both facilitated immediate insight into the product’s properties in correlation to the process parameters. As a second continuous step, spray-drying, converted the CBNs dispersions into powder materials to increase the density and simplify product handling, in addition minimizing self-quenching of the fluorescent properties. As starting materials, phenylenediamine regioisomers were chosen which are conventionally explored via autoclave synthesis. For each regioisomer, two emission wavelength regions appeared in the visible wavelength range. The residence time, temperature, acidic component and initial starting concentration played a significant role in the relative emission intensities concluded from systematic screening. While the resulting materials need further improvement concerning their photo stability and absolute emission intensity, the technological combination presented here is a step towards the tailor-made manufacturing chain of CBNs based on micro-process engineering and continuous flow syntheses at safe high-pressure conditions.

An innovative method for synthesising and functionalising iron oxide nanoparticles (IONPs) with polyethylene glycol (PEG) using a continuous three-phase segmented flow reactor is presented. Integration of synthesis and functionalisation within a single reactor platform eliminates the need for laborious batch post-processing steps, such as washing, separation, and dialysis, significantly reducing processing time and enhancing efficiency. The incorporation of oleic acid during the PEG functionalisation step further improved colloidal stability, resulting in 15 nm nanoparticles that remained stable for months without precipitation. FTIR and TGA confirmed successful functionalisation, while XRD showed the absence of byproducts. The PEG-functionalised IONPs exhibited excellent biocompatibility, as confirmed by in vitro cytotoxicity assays, with cell viability exceeding 80% at biologically relevant concentrations. Importantly, the functionalisation process preserved the nanoparticles’ key magnetic and thermal properties, such as saturation magnetisation, magnetic heating efficiency and photothermal response, which are essential for their application in therapeutic settings. Biomedical applications of these functionalised IONPs were explored across multiple domains. The nanoparticles showed efficient magnetic hyperthermia performance under an alternating magnetic field, making them suitable for cancer treatment via localised heating. Additionally, their photothermal properties were assessed under near-infrared (NIR) irradiation, demonstrating temperature rise proportional to concentration, and hence their potential for dual-mode therapeutic applications. Furthermore, antifungal activity assays revealed PEG-functionalised IONP’s efficacy against Trichophyton rubrum, with complete fungal growth inhibition at specific concentrations, underscoring their potential in pharmaceutical antifungal formulations. The continuous flow process developed offers a robust platform for producing multifunctional nanoparticles tailored for biomedical applications, while ensuring compatibility with industrial-scale production demands.

As a crucial component of catalytic ligands, the synthesis of 1-bromo-3,5-diarylbenzene compounds holds significant value. Herein, we have reported a continuous-flow method for the synthesis of diverse 1-bromo-3,5-diarylbenzene compounds. A novel organomagnesium reagent was prepared via halogen-magnesium exchange between iPrMgCl·LiCl and 2,4,6-tribromoiodobenzene, followed by sequential C–C bond formation with aryl Grignard reagents to afford terphenyl Grignard reagents within 468 s. These intermediates exhibited broad reactivity towards diverse electrophiles and could be directly quenched to afford a series of 1-bromo-3,5-diarylbenzene compounds (16 examples) with isolated yields of 66–90%. This method obviates the need for large excesses of aryl Grignard reagents, avoids the use of noble metal catalysts, and simplifies purification via direct recrystallization. Moreover, a high-performance scale-up synthesis of the precursor for the catalytic ligand was smoothly carried out, demonstrating its practical utility.

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The generation of a novel organomagnesium reagent in a continuous flow reactor and its reaction with aryl Grignard reagents is reported. A series of m-terphenyl compounds have been synthesized, achieving good yields of up to 90% across 21 examples.

Styrene droplets were generated using a coaxial flow droplet microfluidic device. In the self-assembled coaxial flow droplet generation device, styrene was used as the dispersed phase and the aqueous solution containing surfactant was used as the continuous phase to study the generation of styrene droplets. The effects of the two-phase flow rate and surfactant concentration on the droplet size were investigated, and a mathematical correlation formula for predicting the droplet size was obtained by three-dimensional analysis of the experimental values. The results showed that the diameter of the droplet was negatively correlated with the flow rate of the continuous phase and the concentration of surfactant in the continuous phase, and the diameter of the droplet was positively correlated with the flow rate of the dispersed phase. The diameter of styrene droplets produced by coaxial flow droplet generation device ranges from 70.39 μm to 377.09 μm. The predicted values obtained by the correlation formula are in good agreement with the experimental values, with an error within 25%. The successful generation of styrene droplets in the self-assembled coaxial flow device provides the idea for the generation of monodisperse Oil-in-Water droplets.

The hydroconversion of model organosulfur compounds with different formal oxidation states of sulfur (thiophene, dimethyl disulfide, dimethyl sulfoxide, dimethyl sulfone, sulfolane, and dimethyl sulfate) was mimicked under transfer hydrogenation (TH) reaction conditions in supercritical methanol and isopropanol. The reactions were carried out in a continuous flow reactor at 250 °C and 350 °C. At 350 °C, only dimethyl disulfide and dimethyl sulfoxide underwent complete or nearly complete conversion within 5 min of contact time, mainly by reductive cleavage of S–S, S–O, and S–C bonds to form dimethyl sulfide MeSMe and methyl mercaptan MeSH.

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Description

Simple organosulfur compounds with different formal oxidation states of sulfur in their molecules were studied in high-temperature transfer hydrogenation reaction with supercritical methanol and isopropanol in continuous flow mode.

Phenylhydroxylamine (PHA) derivatives are key chemical intermediates of nitrogen-containing organic compounds, however, their selective synthesis is challenging. Using Bayesian optimization, we attempted to streamline the reaction conditions for synthesizing PHAs in a microreactor to improve the yield of the target compound. Based on the results obtained in our previous work, the photoreduction of nitrobenzene was used for the selective synthesis of PHA under slug flow conditions. Furthermore, we examined the key factors responsible for the high synthetic selectivity. The optimization method helped us to optimize the experimental conditions required to achieve a yield of over 90% with only seven synthetic experiments. These results suggest that it is important to achieve a high reaction rate. Furthermore, additional experiments, cyclic voltammetry measurements, and calculations indicated that it is crucial to maintain the high redox potential of PHA under slug flow conditions with ethyl acetate. Finally, a batch reaction of the two phases was attempted to synthesize the target compound in comparison with the results of the flow reaction. Although the target compound was obtained in moderate yield with few byproducts, a prolonged reaction time was required. The flow reaction of the two phases slightly improved the synthesis selectivity and shortened the reaction time. We expect this reaction achieved by the merits of flow reactions to be useful for the synthesis of unstable PHAs.

We report the development of simple solution-phase flow conditions for the scalable synthesis of peptides using in-situ activation as mixed anhydrides, contributing to the synthetic toolbox of available solution-phase flow reactions. This approach has been used for the preparation of a series of diverse dipeptides in plug flow, and then continuous flow conditions (< 10 mmol) were developed and applied to the gram scale synthesis of the hexapeptide linear precursor for the bioactive cyclic peptide segetalin A as further proof of the utility of this approach.

Graphical Abstract

An efficient continuous flow process was developed for synthesizing (E)-O-(3-chloro-2-propenyl)hydroxylamine, a crucial intermediate of clethodim. This continuous flow manufacturing approach encompasses three chemical transformations from the simple and readily accessible material, hydroxylamine hydrochloride. Through a systematic series of screening tests conducted under various flow conditions, the traditional batch synthesis route was successfully simplified. The amide condensation reaction was achieved in just 70 s at room temperature within the flow system. Additionally, the chloroamination step was streamlined using a microreactor, significantly reducing the required reaction time and enhancing heat transfer efficiency. Finally, (E)-O-(3-chloro-2-propenyl)-hydroxylamine was furnished in 70% isolated yield with a purity of 96%, a total residence time of 18 min and 12.84 g/h throughput.

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