Microfluidic Chip Reactor Research Articles

Carbon dioxide hydrate crystallization thickening & morphology in a micro-confined environment for carbon capture & sequestration processes

Carbon dioxide capture and sequestration (CCS) are critical processes that are necessary to mitigate the impacts of climate change. In pipelines used for CCS and for ocean sequestration, the formation of CO2 hydrates can occur and be detrimental to the safety and integrity of the CCS equipment and process. Understanding the crystallization thickening behavior of CO2 hydrates is vital for understanding hydrate formation in CO2 pipelines and in other CCS applications, such as sequestration and CO2 capture or storage. In this study, a microfluidic chip reactor was used to crystalize and thicken CO2 hydrates at the channel walls. The morphology of the CO2 hydrates was visually analyzed and quantified using in situ Raman spectroscopy. Two hydrate layers were consistently observed. An annealed, dense layer of hydrate shared an interface with liquid water, while a porous hydrate layer shared an interface with CO2 gas. Capillary-like pore spaces could be observed in the porous layer, which confirms one proposed mechanism for hydrate film thickening. Subcooling (0.5–1.5 K), pressure (2.51, 3.10 MPa), and flow rate of CO2 (0.167, 1.67 mm3/s) were studied for their impact on the overall CO2 hydrate film thickness over time. Over the ranges of these chosen parameters, only CO2 flow rate was found to have a significant impact on the thickening of CO2 hydrates, and a higher flow rate led to thicker crystalline hydrate films. A first principles mass transfer model for hydrate film thickness was developed and applied to the measurement data collected for overall hydrate film thickness.

Effects of external light in the magnetic field-modulated photocatalytic reactions in a microfluidic chip reactor.

Photocatalytic reactions and their magnetic-field enhancement present significant potential for practical applications in green chemistry. This work presents the mutual enhancement of plasmonic photocatalytic reaction by externally applied magnetic field and plasmonic enhancement in a micro optofluidic chip reactor. The tiny gold (Au) nanoparticles of only a few atoms fixed on the surface of titanium dioxide (TiO2) nanoparticles lead to mutually boosted enhancement photocatalytic reactions under an external magnetic field and plasmonic effects. The dominant factor of adding green light to the photocatalytic reaction leads to the understanding that it is a plasmonic effect. The positive results of adding ethanol alcohol (EA) in the experiments further present that it is a hot electron dominant path photocatalytic reaction that is positively enhanced by both the external magnetic field and plasmonic effects. This work offers great potential for utilizing magnetic field enhancement in plasmonic photocatalytic reactions.

Highly modular PDMS microwave-microfluidic chip reactor for MAOS applications

This work demonstrates the potential of microwave-microfluidics for rapid organic synthesis, incorporating modular flow cells with low-power, variable-MW frequency heating.

Online Monitoring of Isomeric Reaction Intermediates.

Ephemeral intermediates often hold the key to a more detailed understanding of chemical reaction pathways. Online methods to unambiguously identify the structure of such molecular entities, in particular in the presence of multiple isomers, are scarce. This paper presents a methodology that allows real-time monitoring of isomeric solution-phase reaction intermediates of continuous-flow reactions by coupling a microfluidic chip-reactor to a cryogenic ion trap triple mass spectrometer. The technique combines the excellent reaction control associated with microfluidic chips with the unique specificity and sensitivity of infrared photodissociation (IRPD) spectroscopy, which allows for an unambiguous structural assignment of gaseous ions based on their IR fingerprint. It represents a valuable extension to the instrumentation for online-analysis of reactive intermediates and proves particularly valuable whenever the sensitivity of NMR is not sufficient. After a brief description of the experimental approach, illustrative examples are provided to highlight the application of the chip-IRPD setup for mechanistic studies, particularly for stereoselective processes. The article concludes with an outlook on future challenges and perspectives.

Design of the reversible biphasic arrangement in the microfluidic chip reactor for asymmetric hydrogenation reactions

Design of the reversible biphasic system for a practical use in asymmetric hydrogenation performed in a microfluidic chip reactor is reported. Methylacetoacetate (MAA) was transformed to (R)-methylhydroxybutyrate over optically pure (R)-Ru-BINAP as a model reaction. The study was an iteration towards the design, description and optimization of the temperature driven reversible biphasic system in the mixed [NR,222][Tf2N]/methanol/water phase by varying the parameter of the structure of the ionic molecule, starting from [NH4][Tf2N] up to [N14,222][Tf2N]. At temperatures, and other conditions providing high conversions and optical yields, the reaction mixture was monophasic. At lower temperatures, the mixture became biphasic for ionic liquids with long alkyl chains (namely [N14,222][Tf2N]) due to their strong non-polar character. The formed ionic liquid phase accommodated the chiral Ru complex, the water/methanol phase the reaction products. After the reaction, when the mixture was cooled, over 90% of the catalytic complex was kept in the ionic liquid phase. Viscosity and density data were also discussed. It seems the reversible biphasic system offers a way to facilitate the separation of the chiral Ru-complex from the reaction mixture. Due to high sensitivity of the complex to handling conditions, its reuse still requires further optimization.

Stereoselective synthesis of optical isomers of ethyl 4-chloro-3-hydroxybutyrate in a microfluidic chip reactor

Ethyl (R)-4-chloro-3-hydroxybutyrate ((R)-CHBE) is a versatile fine chemistry intermediate. It is used as a precursor in the synthesis of several pharmacologically valuable products, including L-carnitine. It is usually produced by means of stereoselective biotechnology methods in enzymatic reactions. An alternative preparation strategy towards ethyl (R)-4-chloro-3-hydroxybutyrate is based on the asymmetric hydrogenation of ethyl 4-chloro-acetoacetate (ECAA) to the optically pure product ((R)-CHBE) over ((S)-Ru-BINAP) catalytic complex. The reaction conditions were optimised first using (R)-Ru-BINAP yielding the (S)-CHBE isomer. All reactions were performed under continuous regime in a microfluidic chip reactor. Three different solvent phases were employed. The methanol/water phase, the ethanol/water phase, and the [N8,222][Tf2N]/methanol/water phase. The attained conversions were total in all cases already at 408 K. The parameter of enantioselectivity ee was 99.4% towards the (S)-CHBE for the system in which (R)-Ru-BINAP was accommodated in [N8,222][Tf2N]/methanol/water phase. In the case of methanol/water experiment the ee parameter reached 92.5%. For ethanol/water ee was 91.8%. The (R)-CHBE isomer over (S)-Ru-BINAP was obtained with ee = 99.3% in the [N8,222][Tf2N]/methanol/water phase at 408 K. For the reactions leading to (S)-CHBE apparent activation energies were evaluated. They were similar for MeOH/water and EtOH/water (110.5 and 110.7 kJ.mol−1). The apparent activation energies corresponding with the [N8,222][Tf2N]/MeOH/water system were much higher (of about 90 kJ.mol−1) reaching the level of 200 kJ.mol−1. The impact of the molecular structure of the main reactant was negligible as appeared from the comparison with hydrogenation of methylacetoacetate (MAA, ~ 200 kJ.mol−1). The effect of the presence of the [N8,222][Tf2N] ionic liquid on the sum of the activation energy dominated. The effectiveness of the enantioselective synthesis was additionally assessed by nuclear magnetic resonance employing the method of enantioselective complexation of the chiral compound with a chiral solvating agent.

Pervaporation of (R)/(S)-methyl 3-hydroxybutyrate (∑MHB) from a mixture containing an ionic liquid, methanol and Ru catalyst

Complex technologies in the production of fine chemicals bring together various connected processes, each bringing specific green chemistry challenges. A valuable mixture arises in the stereoselective hydrogenation of methyl-acetoacetate (MAA) to (R)- and (S)- methyl 3-hydroxybutyrate (∑MHB) over Ru organometallic complex (R)-Ru/BINAP, and in a “green” tetra-alkylammonium bistriflimide/methanol/water solvent phase. The reaction could be carried out in various arrangements, e.g. in a batch mode, in a continuous stirred-tank reactor, or even in a tubular microfluidic chip reactor. In either case, the valuable optically pure Ru complex has been sought to be effectively separated, and potentially recycled. The ionic liquid phase (tetra-alkylammonium bistriflimide) is intended for selective accommodation of the complex in the reaction mixture and as a green alternative to other solvents. It was the main issue of this work to design a specific separation unit, to construct it, and to optimize its performance towards the efficient separation of ∑MHB from the ionic liquid phase bearing the (R)-Ru/BINAP complex. The unit was developed to be connected with the complex preparation process, employing the microreactor fluid flow platform. The separation part of the overall technology was designed as a membrane pervaporation. The membrane separation proceeded with different feed mixtures combining ∑methyl 3-hydroxybutyrate, methanol, ionic liquid and/or the catalyst. The technique was applied at various temperatures, using the industrial composite PDMS membrane, PERVAP™ 4060 from Sulzer. The feed as well as the pervaporate were analyzed by nuclear magnetic resonance spectroscopy and infrared spectroscopy. The enrichment factor of the ∑MHB with respect to the retentate was 1.24 and the ∑MHB permeate mass flux was 61 g h−1 m−2. In addition, the membrane was characterized by scanning electron microscopy and energy dispersive X-ray microanalysis after the membrane process, showing no sorption of the catalyst into the membrane.

Joining Microfluidics with Infrared Photodissociation: Online Monitoring of Isomeric Flow-Reaction Intermediates.

A cryogenic ion trap vibrational spectrometer is combined with a microfluidic chip reactor in a proof-of-principle experiment on the Hantzsch cyclization reaction forming 2-amino-4-phenyl thiazole from phenacyl bromide and thiourea. First, the composition of the reaction solution is characterized using electrospray-ionization mass spectrometry combined with two-color infrared photodissociation (IRPD) spectroscopy. The latter yields isomer-specific vibrational spectra of the reaction intermediates and products. A comparison to results from electronic structure calculations then allows for an unambiguous structural assignment and molecular-level insights into the reaction mechanism. Subsequently, we demonstrate that isomeric and isobaric ions can be selectively monitored online with low process time, i.e., using a single IRPD wavelength per isomer, as the chip reaction parameters are varied.

Analytical Enzymatic Reactions in Microfluidic Chips

A number of approaches have been proposed and tested to transfer enzymatic reactions into the functional elements of microfluidic chips on the example of the bienzyme bioluminescent reaction involving NAD(P)H:FMN-oxidoreductase and luciferase. Measurement of the catalytic activity of these enzymes (under the influence of pollutants) is the basis of enzymatic bioassay of various liquids. It was found that all of the components of the reaction must be placed in the same cell of the chip to improve the reproducibility of the measurements. The use of starch gel as a carrier for immobilization and gelatin as a scaffold in the reactor of the chip enables the preservation of enzyme activity in the course of sealing the chip at room temperature. It is shown that the components of the reaction should be vigorously stirred in a microfluidic chip reactor to improve the efficiency of the analysis. As a result of the studies, a prototype of microfluidic chip based on the enzymatic bioluminescent reaction is proposed. It is characterized by a detection limit of copper sulfate of 3 μM that corresponds to the sensitivity of traditional lux-biosensors based on living cells. The analysis time is reduced to 1 min, and the analysis can be performed by individuals without special laboratory skills.

Microfluidic Synthesis of tert-Butyl Peresters via KI-Catalyzed Oxidative Coupling of Methyl Arenes and tert-Butyl Hydroperoxide

A green and efficient organic–aqueous two-phase reaction route for the synthesis of tert-butyl peresters by KI-catalyzed C–H oxidation of methyl arenes in a microfluidic chip reactor has been developed. Moreover, a series of tert-butyl perester products were obtained in moderate to good yields under metal-free conditions. A scale-up continuous flow system was constructed to verify the application of this method.

Microfluidic chip reactor and the stereoselective hydrogenation of methylacetoacetate over (R)-Ru-BINAP in the [N8222][Tf2N]/methanol/water mixed phase

Homogeneous asymmetric catalysts represented by organometallics of transition elements reveal very high activity and stereoselectivity in asymmetric hydrogenation of β-ketoesters. Recently, it appeared efficient to use ionic liquids of the [NR222][Tf2N] type for accommodation of the chiral catalytic complex. Even on the industrial scale it is becoming attractive to carry out hydrogenations with such immobilised complexes in a continuous regime in microreactors. Attention was paid to the stereoselective hydrogenation of methylacetoacetate (MAA) to isomeric (R)−(+) or (S)−(−)-methyl-3-hydroxybutanoates over a chiral ([RuCl((R)-BINAP)(p-cymene)]Cl) complex immobilised in the mixed [N8222][Tf2N]/methanol/water solvent phase, and performed inside of a microfluidic chip reactor. It was shown that the reaction could be successfully carried out in such an arrangement with a very high enantioselectivity (above 99%) and at very high conversion of MAA (above 97%). It was proven that the participation of a specific solvent (methanol or the mixture [N8222][Tf2N]/methanol/water) essentially influences the mechanism of the reaction. The solvents actively participate in the re-coordination of the catalytic complex in a series of reactions which is reflected in the values of reaction enthalpies. The specific process output was also evaluated.

Microfluidic synthesis of α-ketoesters via oxidative coupling of acetophenones with alcohols under metal-free conditions

An efficient and novel method for the synthesis of α-ketoesters has been developed via oxidative coupling of acetophenones with alcohols under TBHP/I2/DBU conditions in a microfluidic chip reactor, which has a wide substrate scope, uses a lower dosage of iodine and affords higher product yields in only a few seconds.

Molecular structure effects of [NR,222][Tf2N] ionic liquids on their flow properties in the microfluidic chip reactor—a complete validation study

N-alkyl-triethylammonium bis(trifluoromethanesulfonyl)imides ([NR,222][Tf2N]) ionic liquids (different in the length of their alkyl chain) are well suited for accommodating chiral catalytic organometallics in stereoselective hydrogenation reactions. It appears, particularly in the field of industrial fine chemistry that such transformations might be of high practical importance if performed in a microfluidic reactor space. The inspected group of ionic liquids comprises two distinctive kinds of spatial domain—the ionic and the non-polar one. Due to rising the C/H ratio, the non-polar character becomes more dominant and at a certain level the molecular character resembles rather the alkane than the ionic compound. Such significant structural changes must be in some way reflected in flow properties of these ionic liquids, and their mixtures with other fluids inside of a narrow microreactor channel. The molecules with a straight tail may reveal flow properties very different from those with a twisted chain. The term “very different” expresses a clear deviation from trends expected on the basis of their viscosity and density data measurements. The flow conditions were first optimized for a straight capillary, then the tests were transferred to a microfluidic space of a serpentine character, however of the same volume as the original capillary. The main intention was to adapt the microfluidic reactor chip for practical utilization in reaction systems with various [NR,222][Tf2N] ionic liquids.

Highly selective acylation of ferrocene using microfluidic chip reactor

A rapid and highly selective acylation of ferrocene with various acid anhydrides using microfluidic chip as the reactor is described. The pressure driven glass microreactor was fabricated by standard photolithography and wet etching techniques. High conversions of ferrocene to the corresponding acylferrocenes were achieved at 25 °C and no diacylferrocene was observed in any case.