Journal of Flow Chemistry最新文献

Myristyl-γ-picolinium chloride (MGPC) is an alkyl pyridine quaternary ammonium salt and a popular preservative in injectables such as Depo-Medrol (Methylprednisolone acetate). Herein we describe a successful high-p,T,c chemical intensification of MGPC synthesis from neat myristyl chloride and γ-picoline in continuous flow. The process is atom economical, scalable with low reactor footprint and under optimized conditions, consistently affords MGPC in 45 min (instead of 8–12 h reported in literature for a conventional batch process) with excellent yield (> 90%) and purity (> 99%).

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Synthesis of bio-based monomers via continuous flow ozonolysis of cardanol using a simple tubular reactor is demonstrated. The direct ozonolysis of cardanol produces unique monomer 8-(3-hydroxyphenyl) octanal (HPOA) and heptanal along with several other oxidation products. Maximum 47% yield of HPOA with 54.3% conversion of cardanol was obtained at 0 °C in 9 s. The complete conversion of cardanol was obtained at the ozone to cardanol molar flow ratios greater than 2 at all temperatures varied in the range of -10 °C to 20 °C. Owing to large gas–liquid ratios, the mass transfer limitation for transfer of ozone from gas to liquid was negligible; however, the extent of axial dispersion in the liquid phase was significant at lower liquid flow rates. The non-ideal behavior was incorporated in the axial dispersion model to predict the conversion of cardanol. Examination of kinetic rates by both ideal plug-flow model and plug-flow with axial dispersion model revealed that the reaction is fast and is least influenced by the axial-dispersion in the reactor at prevailing operating conditions. The findings of the current study show that continuous flow technique enables a simple and safer synthesis of high-value bio-based monomers via ozonolysis of cardanol compared to traditional batch methods.

Photochemistry and continuous flow chemistry are synthetic technology platforms that have witnessed an increasing uptake by chemical industries interested in complex organic molecule synthesis. Simultaneously, automation and data science are prominent targets in organic synthesis and in chemical industries for streamlined workflows, meaning hardware-software interaction between operators and devices is crucial. Since undergraduate teaching labs at public-funded research Universities typically (i) lack budget for commercial, user-friendly continuous flow reactors and (ii) do not teach synthetic chemists how to program or interact with reactors, there is a disparity between the skills undergraduates are equipped with and the skills that future industries need. We report a teaching lab project where undergraduates assemble, program and execute a continuous flow photoreactor to realize a multigram-scale photoredox catalyzed oxidation reaction. A palladium-free synthetic access to the starting material was described to further cut costs. Not only does this exercise introduce useful skills in reactor design, programming and wet chemistry (both photochemical and thermal, both batch and flow), it also accommodates both the typical budget and afternoon timeslot (2-3 h) of a teaching lab and can be followed by thin-layer chromatography/color changes without necessarily requiring access to NMR facilities.

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Porphyrin derivatives have found diverse applications due to their attractive photophysical and catalytic properties, but remain challenging to synthesize, particularly at scale. Porphyrin synthesis thus stands to benefit from the more controlled environment, opportunities for efficient optimization, and potential for scale-up available in flow. Here, we have transferred Lindsey porphyrin synthesis into flow, enabling controlled timing for oxidation and neutralization steps and real time monitoring of the reaction mixture with inline UV–Vis analysis. For tetraphenyl porphyrin (TPP), inline UV–Vis showed the presence of protonated TPP, formed due to residual acid. Thus, inline monitoring allowed optimization of the neutralization step to improve yield. Three further porphyrin substrates were produced in flow; in two cases, the yield from inline UV was significantly higher than the yield from post-purification, identifying further yield losses that could be recovered by modifying the purification step. The workflow presented here can be adapted to multiple substrates to systematically optimise porphyrin yield, reducing the time needed to develop scalable routes to these valuable compounds.

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.