Flow Synthesis Method Research Articles

Microwave-assisted continuous flow synthesis of propofol

Herein, we present a breakthrough microwave-assisted continuous flow synthesis method for Propofol, an essential anesthetic recognized by the World Health Organization (WHO). This innovative approach exploits the synergistic potential of two cutting-edge technologies in organic synthesis: microwave irradiation and continuous flow. Using this powerful combination, we have developed an enhanced synthesis process for Propofol. Our method achieves Propofol synthesis in only two steps: Friedel-Crafts isopropylation followed by decarboxylation, with a remarkably short total residence time of 21.25 min and an impressive overall yield of 80% over both steps. Of particular note is the decarboxylation step, which is performed in an environmentally friendly solvent, glycerol, and requires a residence time of only 1.25 min. This step yields an impressive 94% with a throughput of 7.07 g h−1, demonstrating the efficiency and sustainability of our approach.

Optimization and Scale-Up of a Continuous Flow Synthesis of Dapagliflozin

Dapagliflozin is a selective inhibitor of sodium-dependent glucose cotransporter 2 (SGLT2). The traditional synthesis method of dapagliflozin needs ultralow temperature (−78 °C) and is greatly affected by the environment. Here we report a continuous flow synthesis process for dapagliflozin. The mild and efficient synthesis of Br/Li exchange reaction and C-arylation was achieved with the aid of efficient mixing and heat transfer in the microreactor, and the reaction temperature could be increased from −78 °C to −20 °C. The closed environment can reduce the environmental interference of moisture in the ambient air in the methoxy reduction reaction, thereby minimizing the formation of impurities, meeting the quality requirements. The continuous flow synthesis method for dapagliflozin reported in this paper not only greatly shortened the reaction time (from 26 h to 43 min) but also significantly improved the safety of the process and increased the yield. The final product quality is improved, the purity of the product is 99.83%, and the existing scale output is as high as 4.13 kg/day.

Machine-Learning-Guided Discovery of 19F MRI Agents Enabled by Automated Copolymer Synthesis.

Modern polymer science suffers from the curse of multidimensionality. The large chemical space imposed by including combinations of monomers into a statistical copolymer overwhelms polymer synthesis and characterization technology and limits the ability to systematically study structure-property relationships. To tackle this challenge in the context of 19F magnetic resonance imaging (MRI) agents, we pursued a computer-guided materials discovery approach that combines synergistic innovations in automated flow synthesis and machine learning (ML) method development. A software-controlled, continuous polymer synthesis platform was developed to enable iterative experimental-computational cycles that resulted in the synthesis of 397 unique copolymer compositions within a six-variable compositional space. The nonintuitive design criteria identified by ML, which were accomplished by exploring <0.9% of the overall compositional space, lead to the identification of >10 copolymer compositions that outperformed state-of-the-art materials.

Low-temperature flow-synthesis-assisted urethane-grafted zinc oxide-based dental composites: physical, mechanical, and antibacterial responses

A novel way was adopted to graft zinc oxide (ZnO) with urethane-modified dimethacrylate (UDMA) in order to utilize them as reinforcing agents in resin-based dental composites. Experimental novel composites were synthesized having UDMA-grafted and nongrafted ZnO, at a concentration of 0 wt.%, 5 wt.%, and 10 wt.%. The same concentrations of ZnO were also incorporated in Filtek Z250 XT (3 M ESPE, USA). The antibacterial behavior was evaluated against Streptococcus mutans by direct-contact test at one, three, and seven days of incubation. The compressive strength and Vickers microhardness were tested as per ISO 9917 and ISO/CD6507-1, respectively. For abrasive wear resistance, mass loss and roughness average after tooth-brushing cycles of 24,000 at custom-made tooth-brushing simulator were evaluated using noncontact profilometer. Data analysis was carried out using post hoc Tucky’s test and nonparametric Kruskal–Wallis test. Direct contact test revealed that the antibacterial potential of novel and commercial composites was increased with an increase in the concentration of grafted ZnO as compared with nongrafted, whereby the potential was the highest at day seven. There was a significant decrease in compressive strength and Vickers hardness of commercial composites on addition of grafted ZnO while there was no significant difference in the strength of experimental novel composite. The abrasive wear of commercial and experimental composites was within clinical limits. Low-temperature flow-synthesis method was successfully employed to synthesize grafted and nongrafted ZnO. The UDMA-grafted ZnO can be incorporated into dental composites without decreasing their strength and these composites can be used to combat secondary caries.

Continuous-flow synthesis of (E)-2-Hexenal intermediates using a two-stage microreactor system

A flow synthesis method of (E)-2-hexenal intermediates by employing a two-stage microreactor system was reported as an example of autothermal Prins-type reaction. The continuous flow technology not only overcame the low efficiency of batch reactions, it also met the demand for high selectivity and required less consumption of reactants. Temperature monitors of a micro-mixer and a reaction tube covered by thick thermal insulation materials provided an apparent reaction enthalpy of −112 kJ·mol−1 for the generations of hexenal intermediates and by-products. A two-stage reaction platform was therefore developed to enable efficient control of the reaction temperature, which was from 20 °C and 110 °C. Under optimized operating conditions, the yield of (E)-2-hexenal intermediates reached 72%, with a space time yield of 273 kg·h−1 L−1, which was over 1200 times that of a traditional batch reactor with dripping fed reactants. The final yield of (E)-2-hexenal was maintained at 72% after hydrolysis of the intermediates.

Efficient synthesis of lithium rare-earth tetrafluoride nanocrystals via a continuous flow method

As an important upconversion illuminant material, LiREF4 nanocrystals were efficiently synthesized in a continuous reactor with the assistant of a new precursor solution. The employed trioctylamine solvent in the solution had a strong interaction with HF, and helped to avoid the generation of unnecessary solid components as LiF and NH4REF4 during the reaction. A silicon carbide reactor was developed to carry out the synthesis reaction, where LiYF4:Yb,Er/Ho/Tm quickly nucleated in 5 min at 300 °C. The reaction time to successfully prepare 15 nm sized nanocrystals was less than 30 min, and the space-time yield of the flow synthesis method was 14.8 times that of a control group batch reaction. The prepared nanocrystals had a strong illuminant ability, which could find its use in the area of security mark printing.

Novel continuous flow synthesis of Pt NPs with narrow size distribution for Pt@carbon catalysts.

In this work, we report a novel continuous flow synthesis method to achieve ultra-small Pt NPs (2.3 to 2.5 nm) with narrow size distribution. This method expedited the synthesis of Pt NPs without any harsh reducing agent or capping agent. Further these Pt NPs were immobilized on a carbon support in a single step procedure for its application as an electrocatalyst for fuel cells. The synthesized Pt NPs and Pt NPs supported on carbon were analyzed using transmission electron microscopy affirming uniform distribution of Pt NPs throughout the carbon support without aggregation.

Magnesium Chromium Oxide Nanocrystals: Synthesis and Electrochemistry

Chromium oxides with the spinel structure have been predicted to be promising high voltage cathode materials in magnesium batteries. Perennial challenges involving the mobility of Mg2+ and reaction kinetics can be circumvented by nano-sizing the materials in order to reduce diffusion distances, and by using elevated temperatures to overcome activation energy barriers. Herein, ordered 7 nm crystals of spinel-type MgCr2O4 were synthesized by a conventional batch hydrothermal method. In comparison, the relatively underexplored Continuous Hydrothermal Flow Synthesis (CHFS) method was used to make highly defective sub-5 nm MgCr2O4 crystals. When these materials were made into electrodes, they were shown to possess markedly different electrochemical behavior in a Mg2+ ionic liquid electrolyte, at moderate temperature (110 °C). The anodic activity of the ordered nanocrystals was attributed to surface reactions, most likely involving the electrolyte. In contrast, evidence was gathered regarding the reversible bulk deintercalation of Mg2+ from the nanocrystals made by CHFS. This work highlights the impact on electrochemical behavior of a precise control of size and crystal structure of MgCr2O4. It advances the understanding and design of new cathode materials for Mg-based batteries.

Ultrafast microfluidic synthesis of hierarchical triangular silver core-silica shell nanoplatelet toward enhanced cellular internalization

Microfluidic reactors represent a new frontier in the rational design and controllable synthesis of functional micro-/nanomaterials. Herein, we develop a continuous and ultrafast flow synthesis method to obtain triangular silver (tAg) nanoplatelet using a short range two-loop spiral-shaped laminar flow microfluidic reactor, with one inlet flow containing AgNO3, trisodium citrate, and H2O2 and the other NaBH4. The effect of the reactant concentration and flow rate on the structural changes of tAg is examined. Through the same miniaturized microreactor, hierarchical core-shell Ag@SiO2 can be produced with tunable silica shell thickness using one inlet flow containing the as-synthesized Ag nanoparticles together with tetraethyl orthosilicate and the other ammonia. The enhanced cellular internalization efficiency of triangular nanoplatelets by PANC-1 and MCF-7 cells is further confirmed in comparison with the spherical ones. These results not only bring new insights for engineering nanomaterials from microreactors but also facilitate the rational design of functional nanostructures for enhancing their biological performance.

Generation and Cross-Coupling of Organozinc Reagents in Flow.

A versatile flow synthesis method for in situ formation of organozinc reagents and subsequent cross-coupling with aryl halides and activated carboxylic acids is reported. Formation of organozinc reagents is achieved by pumping organic halides, in the presence of ZnCl2 and LiCl, through an activated Mg-packed column under flow conditions. This method provides efficient in situ formation of aryl, primary, secondary, and tertiary alkyl organozinc reagents, which are subsequently telescoped downstream to a Negishi or decarboxylative Negishi cross-coupling reaction. The described method offers access to a variety of C-C bond formations with organozinc reagents that are otherwise commercially unavailable or difficult to prepare under traditional batch reaction conditions.

Electrochemical reduction of carbon dioxide on copper-based nanocatalysts using the rotating ring-disc electrode

A continuous hydrothermal flow synthesis method was used to produce copper(I) oxide nanoparticles, which were used as an electrocatalyst for the reduction of CO2. A rotating ring-disc electrode (RRDE) system was used to study the electroreduction processes, including a systematic study (including quantitative NMR analysis) to identify product species formed at the disc and detected at the ring. In 0.5 M KHCO3 electrolyte with a pH of 7.1, carbon dioxide was found to be exclusively reduced to formate. In the potential range −0.5 to −0.9 V vs the reversible hydrogen electrode (RHE), an active material/glassy-carbon disc electrode was shown to produce formate, with a maximum Faradaic efficiency of 66% (at −0.8 V vs RHE).

Room temperature vanadium dioxide–carbon nanotube gas sensors made via continuous hydrothermal flow synthesis

Vanadium dioxide–carbon nanotube (VO2–CNT) nanocomposite materials were produced via a continuous hydrothermal flow synthesis (CHFS) method. The composites were made in a single step from CHFS using dispersions of commercially available single-walled carbon nanotubes (SWCNTs) or multi-walled carbon nanotubes (MWCNTs) in a metal salt solution (aq.). The room temperature gas sensing characteristics of the VO2-CNT nanocomposites were investigated and compared with sensors of CHFS-made VO2 without added carbon. The VO2-CNT nanocomposites were found to display high sensitivity to H2O vapour, showing excellent potential as humidity sensors. Furthermore, p-type responses to ammonia gas were observed, with the VO2 (no carbon) sensors showing the largest response. Overall, surface composition and microstructure were found to greatly influence sensor responses to H2O vapour and NH3 gas.

Aerosol assisted chemical vapour deposition of hydroxyapatite-embedded titanium dioxide composite thin films

This work describes the first Aerosol Assisted Chemical Vapour Deposition (AACVD) synthesis of photocatalytic titanium dioxide thin films embedded with synthetic hydroxyapatite, [Ca10(PO4)(OH)2], nanoparticles. The hydroxyapatite nanoparticles were prepared using a low temperature continuous hydrothermal flow synthesis method; analysis of the hydroxyapatite powder showed that it was phase pure and that the as-prepared material was made up of nano-needles. The nanoparticles were then embedded into TiO2 coatings using the AACVD technique by suspending them in a solution of the titania precursor (titanium tetra-isopropoxide). Results showed that the hydroxyapatite, although present in very low concentrations in the coatings (not detectable by XRD or Raman spectroscopy), heavily affected their morphology, depending on their concentration in the precursor solution. Tests of the photocatalytic activity of the composite films showed that the inclusion of the hydroxyapatite led to an increase in methylene blue photodegradation (up to 50% higher) and that the materials were photostable. This study shows that TiO2 coatings embedded with hydroxyapatite nanoparticles have potential as highly efficient photocatalysts.

Flow Synthesis of Silver Nanowires for Semitransparent Solar Cell Electrodes: A Life Cycle Perspective.

Silver nanowires (AgNWs) were prepared on a 5 g scale using either the well-known batch synthesis following the polyol method or a new flow synthesis method. The AgNWs were employed as semitransparent electrode materials in organic photovoltaics and compared to traditional printed silver electrodes based on micron sized silver flakes using life cycle analysis and environmental impact analysis methods. The life cycle analysis of AgNWs confirms that they provide an avenue to low-impact semitransparent electrodes. We find that the benefit of AgNWs in terms of embodied energy is less pronounced than generally assumed but that the toxicological and environmental benefits are significant.

Continuous microwave flow synthesis (CMFS) of nano-sized tin oxide: Effect of precursor concentration

Tin oxide (SnO2) nanoparticles exhibit an intense luminescent behavior under UV-light in contrast to the bulk tin oxide and therefore have become focus of many investigations. SnO2 nano-agglomerates were successfully prepared by continuous microwave flow synthesis (CMFS) method using tin chloride pentahydrate as a tin precursor. The effect of concentration of reacting species on the degree of crystallinity, particle size, lattice parameters, morphology, and photocatalytic behavior was probed. Structural and morphological features of the resulting SnO2 nano-structures were examined by using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Brunar Emmett Tellar (BET), Transmission electron microscopy (TEM) and ultra-violet (UV/Visible) spectroscopy. From the XRD spectra the crystal structure of the synthesized product was confirmed as phase pure tetragonal cassiterite type with particle size of 4.43nm. TEM images further confirmed the formation of highly agglomerated nanoparticles, whereas the change in concentration had no appreciable effect on the particle morphology. BET surface area measurements confirmed that the surface area of the SnO2 nanoparticles decreased with increase in Sn precursor concentration. The optical band gap values of SnO2 nanoparticles were calculated to be 3.19eV, which is a red-shift compared with that of the bulk SnO2 (3.6eV). The nano-agglomerates were efficient catalyst for the photodegradation of methylene blue (MB) dye. Our results indicate that the synthesized SnO2 nanoparticles can have potential applications in liquid photovoltaic, photocatalysis and sensors.

Hydrothermal Synthesis and in Situ Powder X-ray Diffraction Study of Bismuth-Substituted Ceria Nanoparticles

Ceria is a widely used material for multiple purposes, e.g., as catalysts, sensors, and solid electrolytes. Substitution of Ce with Bi in nanocrystalline ceria facilitates an even broader field of applications. Here we present an easy, reproducible autoclave-based hydrothermal route for preparing phase-pure nanocrystalline bismuth-substituted ceria as well as a continuous flow synthesis method that is suitable for large-scale production. The produced materials were characterized using a wide range of techniques to understand the synthesis-dependent changes in crystallographic structure, crystallite size, optical properties, type and number of surface adsorbed groups, and overall nanostructure. Furthermore, photodecomposition of a model dye compound (rhodamine B) was performed to investigate the photocatalytic properties of the as-synthesized materials. To investigate the formation mechanisms, in situ powder X-ray diffraction data were measured, revealing that miniscule crystallites of BixCe1–xO2–x/2 forme...

Low-Cost and Fast Production of Nano-Silica from Rice Husk Ash

Silica with nanostructure are the high quality silica that are used in many industry areas. The applications of silica nanostructure frequently depend on physical properties such as morphology and size of structure. Rice husk ash is the waste from biomass power plants and is a high quality, raw material as a silica source. The conventional methods for synthesis of nanosilica from rice husk ash are energy consumption or time consumption. The objective of this work was to investigate the synthesized of nanosilica from rice husk ash via sodium silicate solution. nanosilica particles were obtained via alkaline extraction and a fast acid precipitation method at room temperature by adding inorganic salts and without surfactant or template. The flow synthesis was investigated at ambient temperature, varying the concentration of hydrochloric acid, sodium chloride, and flow-rate while fixing the concentration of sodium silicate. The samples were characterized by field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and X-ray diffraction (XRD). The results revealed that the sodium chloride is significantly inorganic salt for generated nanosilica, with uniform spherical morphology (80-150 nm), without curing or aging time. In the flow synthesis method, the silica nanoparticles, of diameter around 10 nm and aggregate particles of around 50 to 200 nm, were obtained. This method may be applicable to control different grade of silica and can easily scaling up of silica production for different industries.

Core/shell magnetism in NiO nanoparticles

The anomalous appearance of a ferromagnetic moment in nominally antiferromagnetic nanoparticles has been known about since Néel, but never well understood. We present proof of the core/shell model of magnetism in antiferromagnetic NiO nanoparticles (NP) using neutron diffraction. Nickel oxide nanoparticles were produced in a large quantity by a novel continuous hydrothermal flow synthesis method. The antiferromagnetic nature of the nanoparticles allowed the structural and the magnetic diffraction peaks to be completely separated. Using both the microstructure option in "Fullprof" microstructure fitting suite and convolution techniques, we determined the NP consisted of an ordered antiferromagnetic core 5.2(2) nm in diameter surrounded by a disordered shell 0.7(2) nm thick. Further magnetic measurements showed that this disordered shell possess a significant polarisable magnetisation, up to a fifth that of pure nickel. They also indicate that two magnetic transitions occur between 400 and 10 K; around 350 K, there is a broad transition from paramagnetic to a form of superparamagnetism, then near 30 K there is a transition to a higher anisotropy state. Differences in field cooled and zero field cooled hysteresis loops were found, though with no evidence of exchange bias effects.

Aerosol flow synthesis of N, Si-codoped TiO2 hollow microspheres with enhanced visible-light driven photocatalytic performance

Abstract In this study, porous N, Si-codoped TiO2 hollow microsphere photocatalysts have been prepared by a facile aerosol flow synthesis method. The prepared photocatalysts were characterized by XRD, SEM, TEM, UV–vis DRS, and XPS. The results indicated that both nitrogen doping and formation of Ti O Si bond happened in the N, Si-codoped TiO2 hollow microspheres, leading to an enhanced visible-light driven photocatalytic performance on degradation of salicylic acid compared with pure TiO2 and single N or Si doped TiO2 counterpart catalysts.

Highly controlled crystallite size and crystallinity of pure and iron-doped anatase-TiO2nanocrystals by continuous flow supercritical synthesis

Abstract