Continuous Flow Microreactor System Research Articles

Homogeneous continuous flow nitration of O-methylisouronium sulfate and its optimization by kinetic modeling.

Nitration of O-methylisouronium sulfate under mixed acid conditions gives O-methyl-N-nitroisourea, a key intermediate of neonicotinoid insecticides with high application value. The reaction is a fast and highly exothermic process with a high mass transfer resistance, making its control difficult and risky. In this paper, a homogeneous continuous flow microreactor system was developed for the nitration of O-methylisouronium sulfate under high concentrations of mixed acids, with a homemade static mixer eliminating the mass transfer resistance. In addition, the kinetic modeling of this reaction was performed based on the theory of NO2 + attack, with the activation energy and pre-exponential factor determined. Finally, based on the response surface generated by the kinetic model, the reaction was optimized with a conversion of 87.4% under a sulfuric acid mass fraction of 94%, initial reactant concentration of 0.5 mol/L, reaction temperature of 40 °C, molar ratio of reactants at 4.4:1, and a residence time of 12.36 minutes.

Efficient lignin depolymerization by continuous flow microreactor-assisted electrochemical advanced oxidation in water/co-solvent system

The employment of EAOP using a continuous flow microreactor for efficient lignin depolymerization under ambient conditions.

Scaling-up of carbon dots hydrothermal synthesis from sugars in a continuous flow microreactor system for biomedical application as in vitro antimicrobial drug nanocarrier

ABSTRACT Carbon dots (CDs) are a new class of nanomaterials exhibiting high biocompatibility, water solubility, functionality, and tunable fluorescence (FL) property. Due to the limitations of batch hydrothermal synthesis in terms of low CDs yield and long synthesis duration, this work aimed to increase its production capacity through a continuous flow reactor system. The influence of temperature and time was first studied in a batch reactor for glucose, xylose, sucrose and table sugar precursors. CDs synthesized from sucrose precursor exhibited the highest quantum yield (QY) (175.48%) and the average diameter less than 10 nm (~6.8 ± 1.1 nm) when synthesized at 220°C for 9 h. For a flow reactor system, the best condition for CDs production from sucrose was 1 mL min−1 flow rate at 280°C, and 0.2 MPa pressure yielding 53.03% QY and ~ 6.5 ± 0.6 nm average diameter (6.6 mg min−1 of CDs productivity). CDs were successfully used as ciprofloxacin (CP) nanocarrier for antimicrobial activity study. The cytotoxicity study showed that no effect of CDs on viability of L-929 fibroblast cells was detected until 1000 µg mL−1 CDs concentration. This finding demonstrates that CDs synthesized via a flow reactor system have a high zeta potential and suitable surface properties for nano-theranostic applications.

Heterogeneous nitration of nitrobenzene in microreactors: Process optimization and modelling

Aromatic nitration with mixed acid is an important step in the industrial synthesis of basic industrial chemicals, while the highly exothermic and heterogeneous nature of the reaction renders difficulties in achieving high safety and efficiency. In this work, a continuous flow microreactor system was developed for the nitration of nitrobenzene. Under the premise of high conversion and selectivity, the reaction time and temperature were reduced from more than 2 h and 80 ℃ in industrial operation to 10 min and 65 ℃ in microreactors, respectively. The reaction mechanism was verified that the reaction took place not only in the bulk aqueous phase but also at the phase interface. The kinetic parameters were then determined based on the assumption of pseudo-homogeneous reaction mixture. These findings may shed important insights into the high degree of controllability of nitration for a better process design and reactor optimization.

Kinetics of glyoxal oxidation by nitric acid in a capillary microreactor

Aiming at solving the problems of long operation periods, low selectivity, and low safety in the traditional batch reactor, a method of oxidation reaction of glyoxal with nitric acid through a continuous flow microreactor is proposed, with high selectivity. The method utilizes the excellent performance of mass and heat transfer in the microreactor, to improve the reaction efficiency, selectivity, and safety. The effects of the mixing performance, the molar ratio of reactants, temperature, residence time, and mass fraction of nitric acid on the oxidation of glyoxal with nitric acid are investigated, and the optimum reaction conditions are determined. The glyoxylic acid yield can reach 81.6% while the selectivity is 92.4% with the set residence time of only 7.9 min at 68 ℃ (the molar ratio of nitric acid to glyoxal is 1.4, sodium nitrite to glyoxal is 0.15, hydrochloric acid to glyoxal is 0.2, and the mass concentration of nitric acid is 35%). The apparent kinetic model of the oxidation reaction of glyoxal with nitric acid in a microchannel reactor is established. By precisely controlling the reaction temperature and residence time of the continuous flow microreactor system, the apparent reaction rate constants, pre-exponential factor, and activation energy of glyoxal oxidation to glyoxylic acid by nitric acid are obtained. This work paves the way for the promotion of the synthesis of glyoxylic acid in a microreactor by the continuous flow chemistry system.

Kinetic study on the reaction routes in the oxidation of K/A oil by nitric acid with microreactors

A continuous-flow microreactor system was applied to evaluate the detailed kinetics of the reaction routes involved in the oxidation of K/A oil by nitric acid, which is essential to obtain an in-depth comprehension of complex reaction mechanisms, having important guiding significance for the two-stage temperature control strategy. 6-hydroxyimino-6-nitrohexanoic acid (AMNA) was identified as a major intermediate and its presence was confirmed through UPLC-MS and 1H NMR characterizations. A multi-step reaction kinetic model was developed, revealing good prediction with the experimental results. Finally, the model was applied to investigate the effects of operating parameters on the reaction routes distribution and reaction rate. The simulation results showed that high temperature and nitric acid concentration contributed to high selectivity of adipic acid through promoting the AMNA route, and greatly reduced the required reaction time, indicating that the accurate control over the conditions in this rapid and strongly exothermic process was of paramount importance.

Improving the reaction efficiency of condensation amidation of piperazine with benzoic acid based on kinetics study in microreactors

Here we developed a continuous flow microreactor system to synthesis N-benzoylpiperazine, which is an important intermediate of novel nootropic Sunifiram. And the kinetics of the condensation amidation of piperazine and benzoic acid using HATU as coupling reagent was revealed in microreactor. A kinetic model was established, all the reactions kinetics parameters, including the reaction order of each reactant, rate constants, pre-exponential factors and activation energies were acquired. With this model the selectivity vs. reaction temperature/molar flow ratio were obtained to help understand this kind of reaction and further optimize operating conditions. Under the condition of using equivalent piperazine, 95.6% of selectivity and 91.2% of yield were obtained in microreactor with 50 s. To further expand the scope of carboxylic acid, cyclopropanecarboxylic acid was tried as acylating agent, and 92.8% of selectivity and 86.1% of yield were obtained in microreactor.

Enhanced Hydroformylation in a Continuous Flow Microreactor System

A microreactor system consisting of a honeycomb microreactor and microtubing was proposed to enhance the Rh-biphephos catalyzed hydroformylation of 1-hexene. The effects of various reaction paramet...

Compact Steam-Methane Reforming for the Production of Hydrogen in Continuous Flow Microreactor Systems

The implementation of fuel cell deployment requires efficient conversion of fuels into hydrogen in a distributed energy system. Fortunately, continuous flow and microreactor technology provide unique opportunities for the portable production of hydrogen. This study focuses on determining the operation space for a thermally integrated methane reforming system, thereby providing a theoretical basis for the design and optimization of such systems. The steam-methane reforming over rhodium coupled with methane combustion over platinum in a thermally integrated microchannel reactor arranged with rectangular-shaped protuberances was studied numerically in order to improve its operability and stability. Computational fluid dynamic simulations were carried out with detailed reaction mechanisms to identify conditions for the maximum hydrogen yield and the highest output power. Various operating lines were presented, and various performance metrics were evaluated accordingly. The results indicated that the efficient production of hydrogen is made possible through improving transport performance for highly active catalysts. The flow disturbance elements designed for the reactor are of great benefit to intensification of the reforming process. There exists a trade-off between fuel utilization and output power. Autothermal operation advantages from improved transport performance in small physical dimensions were demonstrated for the system, but careful thermal management is always necessary to ensure its efficient and stable operation. The thermal conductivity of the wall separating the exothermic and endothermic reactions plays a significant role in determining the performance of the system. Highly active catalysts are required to intensify the overall reforming process and to achieve efficient thermal management. Adjustment of fluid velocities can serve as a convenient means to achieve efficient operation of the system.

Identification of kinetic models of methanol oxidation on silver in the presence of uncertain catalyst behavior

AbstractCatalytic oxidation of methanol to formaldehyde is an important industrial process due to the value of formaldehyde either as a final product or as a precursor of numerous chemicals. The study of kinetics in this system is hindered by sources of uncertainty that are inherently associated to the nature and state of the catalyst (e.g., uncertain reactivity level, deactivation phenomena), the measurement system and the structure of the kinetic model equations. In this work, a simplified kinetic model is identified from data collected from continuous flow microreactor systems where catalysts with assorted levels of reactivity are employed. Tailored model‐based data mining methods are proposed and applied for the effective estimation of the kinetic parameters and for identifying robust experimental conditions to be exploited for the kinetic characterization of catalysts with different reactivity, whose kinetic behavior is yet to be investigated.

Continuous flow synthesis of some 6- and 1,6-substituted 3-cyano-4-methyl-2-pyridones

In this study, six 6- and 1,6-substituted-3-cyano-4-methyl-2-pyridones were synthesized in a continuous flow microreactor system. The syntheses were realized at room temperature and the obtained results were compared to those achieved within classical syntheses. In order to optimize the continuous flow syntheses and increase the yield of the products, the retention time in the microreactor was varied by changing the flow rates of the reactant solutions. Furthermore, the reaction was optimized for 3-cyano-4,6-dimethyl-2- -pyridone and 3-cyano-6-hydroxy-4-methyl-2-pyridone, which are comercially important in the pharmaceutical and dye industries. Both 2-pyridones were obtained in satisfactory yield of circa 60 % in less than 10 min. The resulting compounds were characterized by their melting points, FT-IR, 1H-NMR and UV?Vis spectra. The efficiency of the presented method for the synthesis of 2-pyridone-based molecules has promising potential for industrial production.

Continuous flow microreactor for protein PEGylation.

PEGylation is increasingly being utilized to enhance the therapeutic efficacy of biopharmaceuticals. Various chemistries and reaction conditions have been established to synthesize PEGylated proteins and more are being developed. Both the extent of conversion and selectivity of protein PEGylation are highly sensitive to process variables and parameters. Therefore, microfluidic-based high-throughput screening platforms would be highly suitable for optimization of protein PEGylation. As part of this study, a poly-dimethylsiloxane-based continuous flow microreactor system was designed and its performance was compared head-to-head with a batch reactor. The reactants within the microreactor were contacted by passive micromixing based on chaotic advection generated by staggered herringbone grooves embedded in serpentine microchannels. The microreactor system was provided with means for on-chip reaction quenching. Lysozyme was used as the model protein while methoxy-polyethylene glycol-(CH2)5COO-NHS was used as the PEGylation reagent. Full mixing was achieved close to the microreactor inlet, making the device suitable for protein PEGylation. The effect of mixing type, i.e., simple stirring versus chaotic laminar mixing on PEGylation, was investigated. Higher selectivity (as high as 100% selectivity) was obtained with the microreactor while the conversion was marginally lower.

Synthesis of benzaldehyde by Swern oxidation of benzyl alcohol in a continuous flow microreactor system

Preparation of benzaldehyde by Swern oxidation of benzyl alcohol was carried out in a continuous flow microreactor system. Dimethyl sulfoxide (Me2SO) was used as oxidizing agent and oxalyl chloride or p-toluenesulfonyl (p-TsCl) chloride was used as the activating agent. Benzyl alcohol was oxidized to benzaldehyde by the Me2SO-activating agent mixture in the continuous flow microreactor system. The optimized reaction conditions of the Swern oxidation were as follows: oxalyl chloride was used as the activating agent; the mole ratio of Me2SO, oxalyl chloride, and benzyl alcohol was 4:2:1; the ow rate of Me2SO was 1.5 mL/min; the reaction temperature was 15 length of delay loop was 1.5 m; a Caterpillar Split-Recombine Micro Mixer was used; and all of the experiments were completed at atmospheric pressure. The yield of benzaldehyde can reach 84.7% with selectivity of 98.5%. Due to the small reactor volume and short residence times, the Swern oxidation of benzyl alcohol in a continuous flow microreactor system can be operated at nearly room temperature (5–19 ℃) instead of –70 ℃ in a batch reaction, with residence time of reactants in microreactors in milliseconds instead of several hours in a batch reaction.

Direct synthesis of acetic acid by simultaneous co-activation of methane and CO2 over Cu-exchanged ZSM-5 catalysts

The ultimate goal of this study is the development of a new strategy to exploit methane and carbon dioxide resources more efficiently and cleanly. Due to the high stabilities of both methane and CO2, simultaneous CH bond activation of methane and CO2 is one of the toughest challenges in catalysis. Formation of acetic acid was achieved under the continuous flow micro-reactor system by the concurrent feed of methane and carbon dioxide over Cu loaded M+-ZSM-5 catalysts (M=Li+, Na+, K+ and Ca++). The formation of acetic acid was observed in the temperature regime of 425–525°C with a co-feed of CO2 and CH4, under low space velocity of 360mlh−1 based on methane. Compared to Cu0-H-ZSM-5, the M+-ZSM-5 catalyst showed remarkable increment in the formation rate of acetic acid, and the catalytic efficiency was in order K > Na > Ca > Li. The obtained results indicated that the M+ assists in enriching surface active CO2 in the form of carbonates and subsequently reacted with the homolytic activated CH over Cu0-H-ZSM-5. Gathering Cu0 and M+, the Cu0-K-ZSM-5 catalyst showed the highest formation rate of acetic acid (395μ mole gcat−1h−1) at steady state, for 10h time-on-stream at 500°C.

Continuous formation of a seed layer and vertical ZnO nanowire arrays enabled by tailored reaction kinetics in a microreactor

ZnO nanowires (NWs) are gaining widespread popularity due to their many unique physical and chemical properties. The hydrothermal process is the most commonly used approach to prepare vertical ZnO NW arrays. Its fundamental issues are the rather slow deposition rate and the variation of reactant concentrations as a function of time. In this study, we employed a continuous flow microreactor and deposition system to prepare both a ZnO seed layer and vertical ZnO NW arrays continuously by simply tuning the flow rate of reactant solutions. The change in flow rate allows reaction kinetics to be selectively tuned, resulting in the generation of molecular zinc species and colloidal ZnO nanocrystals at a high and low flow rate, respectively. The molecular zinc species constitute the seed layer at the high flow rate, and subsequently the colloidal ZnO nanocrystals contribute to the growth of ZnO NWs at the low flow rate. Since the direct delivery of the controlled building blocks on the substrate prevents the formation of homogeneously induced ZnO particles, we were able to obtain highly uniform ZnO NW arrays, with a growth rate as fast as 240 nm min−1, which is significantly higher than typical growth rates from gas-phase or batch hydrothermal processes. Based on the growth mechanism study, the dimensions of the vertical ZnO NW arrays were varied, leading to an aspect ratio of the NWs up to 23. The advantages of our system were highlighted by preparing a high-quality heterogeneous surface having both hydrophilic and hydrophobic nature on one substrate. These results demonstrate the capability of the continuous flow microreactor and deposition system in efficiently preparing functional vertical ZnO NW arrays.

ChemInform Abstract: Multistep Synthesis of Amides from Alcohols and Amines in Continuous Flow Microreactor Systems Using Oxygen and Urea Hydrogen Peroxide as Oxidants.

AbstractThe oxidation of alcohols (I) in a packed‐bed microreactor followed by oxidative amidation of resulting aldehydes with amines (II) in a spiral‐channel microreactor leads to a wide range of amides (III).

ChemInform Abstract: Generation and Reactions of Pyridyllithiums via Br/Li Exchange Reactions Using Continuous Flow Microreactor Systems.

AbstractA continuous flow microreactor method for generating and carrying out reactions on pyridyllithiums is developed.

Generation and Reactions of Heteroaromatic Lithium Compounds by Using In-Line Mixer in a Continuous Flow Microreactor System at Mild Conditions

A lithium–halogen exchange reaction procedure was applied to introduce electrophilic substituents to the heteroaromatics, which exhibited potential in the syntheses of pharmaceutical intermediates. In this contribution, generation and reactions of heteroaromatic lithium compounds were successfully accomplished at 10 °C in a continuous flow microreactor equipped with an in-line mixer. Extensive reaction results revealed that such a synthetic method was widely applicable for different kinds of heteroaromatics with various substituents. All results highlighted that the lithium–halogen exchange reaction for large-scale syntheses might be realized by microreactor systems.

Generation and Reactions of Pyridyllithiums via Br/Li Exchange Reactions Using Continuous Flow Microreactor Systems

A continuous flow microreactor method for generating and carrying out reactions on pyridyllithiums has been developed based on Br/Li exchange reactions of bromopyridines and dibromopyridines. The reactions can be carried out without using cryogenic conditions by virtue of short residence times and efficient heat transfer, while very low temperatures such as –78 or –110°C are required for conventional batch macro methods. Moreover, sequential introduction of two different electrophiles has been successfully achieved using dibromopyridines in an integrated flow microreactor system composed of four micromixers and four microtube reactors.

Multistep synthesis of amides from alcohols and amines in continuous flow microreactor systems using oxygen and urea hydrogen peroxide as oxidants

By integrating a heterogeneous oxidation step, gas–liquid separation, and an oxidative amidation reaction to form a continuous system, a multistep synthetic protocol has been demonstrated to produce amides under mild conditions using alcohols and amines as the starting materials. The use of inexpensive oxygen and urea hydrogen peroxide as the only oxidants affords an economical and adaptable synthetic route for amides.