Journal of Flow Chemistry最新文献

The emergence of High-Throughput Experimentation (HTE) as a powerful tool for reaction discovery and optimization is changing the way organic chemists are designing their experiments. It is a fantastic way to largely investigate a reaction, in a minimum of time and reagent consumption. However, HTE needs to be accessible to a wide audience for a full implementation in academic and industrial sectors. In that context, developing accessible solid dosing methodologies for submilligram dispensing is necessary. This paper aims at proposing robust mass enhancers solutions for nanomole scale dosing applicable to HTE campaigns.

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Recently demonstrated as a novel reaction screening technology, the stop-flow micro-tubing (SFMT) reactors amalgamate features from continuous micro-flow and conventional batch reactors, resulting in a more logical and rigorous synthesis approach. When compared to traditional batch reactors, SFMT provides a safer and more efficient alternative, particularly suitable for chemical reactions under drastic conditions. The incorporation of commercially available transparent micro-tubing into SFMT makes it an excellent choice for light-mediated reactions, ensuring more uniform exposure to light. And SFMT stands apart from continuous-flow reactors by offering a notably convenient screening approach that is unrestricted by residence time and reactor size, while also effectively eradicating the risk of cross-contamination. The successful reactions developed within the SFMT reactor can be easily translated to continuous-flow synthesis for large-scale production. Overall, the SFMT reactor system exhibits similarities to continuous-flow reactors while surpassing batch reactors, especially for reactions involving gas reagents and/or requiring light illumination. This review aims to provide a comprehensive survey of the synthetic application of SFMT.

Nowadays ε-caprolactone, the monomer of biodegradable polycaprolactone, is mainly produced via the strong exothermic Baeyer–Villiger oxidation of cyclohexanone in semi-batch reactors. In this work, the continuous synthesis of ε-caprolactone was conducted in a self-designed microreactor system to address its strong exothermic feature, resulting in a cyclohexanone conversion of 90.3% and an ε-caprolactone yield of 82.6%. Analysis using a liquid chromatography equipped with high resolution time-of-flight mass spectrometer suggested that the byproducts mainly consist of ε-caprolactone oligomers in the form of dimer, trimer, and tetramer. Such oligomers were produced via hydrolysis of ε-caprolactone, followed by esterification of the hydrolysis product, 6-hydroxyhexanoic acid. Kinetic studies suggest that the hydrolysis reaction orders for ε-caprolactone and water are 0.75 and 2.52, respectively, while dimerization of 6-hydroxyhexanoic acid is a zero-order reaction. The activation energies of the hydrolysis and dimerization were ~ 77.5 kJ·mol⁻¹ and ~ 55.4 kJ·mol⁻¹, respectively. Density functional theory calculations revealed the significant catalytic effect of acetic acid on both side reactions, where the dimerization of 6-hydroxyhexanoic acid proceeds through an alkoxy pathway.

Generally, chemical engineering students get well acquainted with the batch synthesis of various active pharmaceutical ingredients, however, only tiny focus is provided to undergraduates on the topic of flow chemistry. In this paper, we report that students participating in the chemical engineering BSc course at the Budapest University of Technology and Economics were encouraged to perform the flow synthesis of paracetamol, a common pain painkiller. Two different synthetic routes for the continuous production of paracetamol were investigated and compared the batch and flow methods. Thus, these experiments allowed the students to discover flow chemistry for themselves under supervision: how to set up a flow system, how to carry out a reaction continuously, and to experience the advantages of flow chemistry over batch synthesis. In addition, students also got familiar with in-line Fourier transform infrared spectroscopy, as one of the reactions was monitored in real-time.

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The educational manuscript covers the field of continuous flow synthesis of paracetamol supplemented with in-line Fourier transform infrared spectroscopy, which was developed for undergraduate students in the chemical engineering BSc course at the Budapest University of Technology and Economics

The combination of ultrasound and microreactors for the synthesis of nanomaterials is becoming increasingly popular, but effectively altering the ultrasonic field at the microscale to control the crystallization process remains a challenge. Herein, we investigated numerically and experimentally the effects of the ultrasonic field on the synthesis of boron-doped carbon nitride supported silver nanoparticles based on our homemade ultrasound-assisted coiled flow inverter microreactor (UCFIR). Specifically, the ultrasound promotes the radial mixing in the coiled flow inverter microreactor, even under low Reynolds number 10, resulting in better control over the crystallization process. The effects of key parameters, such as ultrasonic field distribution and ultrasonic power, on the particle size and size distribution of Ag/B-g-C₃N₄ have been demonstrated. The results show that when the ultrasound transducer is positioned on the ‘abc’ sides, the Ag/B-g-C₃N₄ with small and uniform Ag particles (4.12 ± 1.12 nm) can be obtained. As ultrasound power increased (0–176 W) and residence time decreased (17.5–140 s), the size of silver nanoparticles decreased, and their distribution narrowed.

Owing to enhanced light-matter interactions and unique optical properties, plasmonic metal nanostructures have garnered extensive research interest and use in wide range of applications. A 3D-printed device for the synthesis of seed-mediated anisotropic gold (Au) nanoparticles (NPs) by droplet-based method is demonstrated. The miniaturized device was used to synthesize Au NPs by using three different reducing agents of different concentrations at two different flow rates and study the evolution of morphology of NPs. The device channel geometry and configuration allowed on-chip chemical syntheses of Au nanomaterials with good uniformity in shape and size. XRD and zeta potential measurement confirmed face-centered cubic structure and negative  surface charge of the synthesized nanomaterials. TEM studies confirmed flower-, urchin- and spindle-shaped morphologies of Au NPs synthesized on using different concentrations of reducing agent. Additionally, computational study to deduce the residence time of the droplets in the device and estimate the electric field distribution around the anisotropic Au NPs is also shown.

In this paper we report a [2 + 2] cycloaddition reaction between ketenes and benzils, characterized by an unusual double photochemical activation triggered by visible light. Employment of a flow system and optimization of reaction conditions through Design of Experiments resulted in moderate to good yields of the corresponding β-lactones. A thorough computational analysis allowed to elucidate the mechanism of the reaction and justify the observed diastereoselectivity. The reaction was also successfully tested with mixed benzils, showing complete regioselectivity.

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We investigated the flow acetalization of aldehydes and THP protection of alcohols using sulfonic acid-functionalized silica gel having hydroxy moiety (HO-SAS) as the solid acid catalyst. The reaction both aliphatic and aromatic aldehydes reacted with methanol within 5 min of residence time to give acetalization product in good to excellent yield. THP protection of primary, secondary, and tertiary alcohols proceeded well to the corresponding products. Both reactions did not require a neutralization process. Scalable syntheses were also achieved with continuous operation. The deprotection reactions were also effective using HO-SAS packed flow reactors.

Micro-distillation is one of the unit operation technologies that are looking toward innovation through on-site and on-demand production system. In this study, a simple structure microdistillator consisting of some plates was applied to reactive distillation, and its potential was investigated. As a target reaction, the heterogeneous esterification between acetic acid and methanol using a solid acid catalyst was employed. The effects of feedstock supply rate, feedstock composition, and device temperature on operation stability and conversion were examined. By controlling the feedstock supply rate and temperature properly, a stable operation with a conversion of approximately 100% was successfully achieved. The amount of methyl acetate produced per weight of catalyst was greater in the reactive distillation using a microdistillator than in the batch reaction, soon after the start of the reaction. Thus, it was demonstrated that the reactive distillation using a microdistillator was able to achieve highly efficient reactions with short reaction time and small amounts of catalyst.

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A vicinal diamine motif can be found in numerous natural compounds and pharmaceuticals, making it an important synthetic target. Herein, we report a telescoped synthesis of vicinal diamines under continuous flow conditions. This approach involves the electrochemical aziridination of alkenes with primary amines, followed by the strain-release driven ring-opening using various nitrogen nucleophiles. The efficacy of the developed method was demonstrated through the synthesis of diverse symmetrically and non-symmetrically substituted vicinal diamines, as well as vicinal amino azides, which can be further hydrogenated to diamines in flow. Additionally, O-centered nucleophiles were employed for the ring-opening of aziridines in our telescoped synthesis, yielding vicinal amino ethers and alcohol. This process offers a streamlined and efficient pathway for the direct synthesis of valuable products from readily available starting materials, bypassing the isolation of unstable aziridine intermediates.

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