Continuous Flow Catalysis Research Articles

A Telescoped Photo-/Organo-Catalyzed Cross Dehydrogenative Coupling (CDC) between Glycine Derivatives and Ketones to Afford Nonproteinogenic Amino Acids (NPAAs) Enabled by Heterogeneous Continuous Flow Catalysis

A Telescoped Photo-/Organo-Catalyzed Cross Dehydrogenative Coupling (CDC) between Glycine Derivatives and Ketones to Afford Nonproteinogenic Amino Acids (NPAAs) Enabled by Heterogeneous Continuous Flow Catalysis

Fibrous catalyst based on atomic Pd and N-doped holey graphene functionalized cotton fiber for continuous-flow reaction

Continuous-flow catalysis bridges the gap between bench-scale laboratories and production-scale factories and thus should be a green and promising technology for the manufacture of value-added chemicals. Here, we present the construction of a continuous-flow catalytic system by integrating a tubular reactor with novel catalytic fibers, which are comprised of single-atomic Pd (Pd1) and nitrogen-doped holey graphene (NHG) functionalized cotton fibers (CFs). Due to the loosely packed structure, highly exposed dual-active sites (i.e., single-atomic PdN4 sites and activated C sites in the NHG carbocatalyst) of the CF@(Pd1/NHG) catalytic fibers, the corresponding flowing system exhibites remarkably high catalytic performance (activity and durability) and processing rate in organic reactions, including oxidative hydroxylation of phenylboronic acid and reduction of nitroarenes. Typically, the processing rate of the catalytic system toward 4-nitrophenol (a representative nitroarene) reduction can reach up to 2.46 × 10−3 mmol·mg−1·min−1, significantly higher than that of those packing catalysts reported in recent years.

The efficient degradation of carbamazepine by Cu-Fe bimetallic composite carbon derived from the waste cation exchange resins: Mechanism, ecotoxicity, and continuous flow catalysis

The Cu-Fe bimetallic composite carbon (CuFeO2@CR) was synthesized by using the waste cation exchange resins as the carbon source to degrade carbamazepine (CBZ) by activating peroxymonulfate (PMS). Results found that 91.3 % of CBZ was degraded under the optimal condition ([PMS] = 0.2 g/L, [CuFeO2@CR] = 0.3 g/L, T = 25℃). CuFeO2@CR could efficiently degrade CBZ at pH 3.03–9.02 and maintain the degradation at 83.6 % in the fifth cycle. The reactive oxygen species (ROS) were SO4•−, •OH, and 1O2 with the relative contribution of 35 %, 29 %, and 36 %, respectively. DFT calculation demonstrated that CuFeO2@CR exhibited a preferential affinity for PMS and greater transfer electrons capacity than CR. Three reaction pathways were proposed in the CuFeO2@CR/PMS system, and the degradation could effectively reduce the toxicity into non-toxic. The continuous flow catalytic experiment indicated the promising application in the treatment of antibiotic wastewater. This work provides guidance and theoretical support for CBZ degradation mechanisms.

Catalytic membrane with in situ formed gold nanoparticles via catechol redox chemistry for continuous flow catalysis

This work focuses on the development of catalytic membrane with gold nanoparticles (Au NPs) as the active phase for a comparative assessment of continuous flow catalytic reduction of 4-nitrophenol (4-NP). However, Au NPs are prepared in a way that relies mainly on toxic reagents and immobilization on the membrane surface is still dominated by deposition, which poses a risk of leakage. We reported a green method to immobilize and reduce Au NPs on membrane surface in situ using polymer brushes containing catechol groups. Scanning electron microscopy (SEM) and x-ray photoelectron spectroscopy (XPS) observations showed that the Au3+ had been reduced to Au NPs and were uniformly distributed on the PAN-PDAu membrane surface without obvious agglomeration. Under the dynamic flow mode, the PAN-PDAu membrane showed strong catalytic activity and stability for the reduction of nitroaromatic compounds. A possible mechanism the catalytic reduction of 4-NP was explored via density functional theory analysis, electron paramagnetic resonance (EPR) and liquid chromatography-mass spectrometry (LC-MS), which verified that the catechol groups contributed to the catalytic reduction reaction of 4-NP. In addition, the PAN-PDAu membrane also had an excellent antibacterial performance. This study provides new insights for the green design of catalytic membrane for industrial applications.

De novo construction of amine-functionalized metal-organic cages as heterogenous catalysts for microflow catalysis

Microflow catalysis is a cutting-edge approach to advancing chemical synthesis and manufacturing, but the challenge lies in developing efficient and stable multiphase catalysts. Here we showcase incorporating amine-containing metal-organic cages into automated microfluidic reactors through covalent bonds, enabling highly continuous flow catalysis. Two Fe4L4 tetrahedral cages bearing four uncoordinated amines were designed and synthesized. Post-synthetic modifications of the amine groups with 3-isocyanatopropyltriethoxysilane, introducing silane chains immobilized on the inner walls of the microfluidic reactor. The immobilized cages prove highly efficient for the reaction of anthranilamide with aldehydes, showing superior reactivity and recyclability relative to free cages. This superiority arises from the large cavity, facilitating substrate accommodation and conversion, a high mass transfer rate and stable covalent bonds between cage and microreactor. This study exemplifies the synergy of cages with microreactor technology, highlighting the benefits of heterogenous cages and the potential for future automated synthesis processes

Accelerated Diffusion of a Copper(I)-Functionalized COF Packed Bed Reactor for Efficient Continuous Flow Catalysis.

Flow chemistry provides a neo-orientation for the research and development of chemical technology, in which heterogeneous continuous catalysis based on packed beds can realize rapid separation and recycling. However, options for heterogeneous catalysts are still limited. In this work, we gradually grow covalent organic frameworks (COFs, TpBpy) on the surface of a silica gel (SiO2)-supported substrate to obtain a stable copper(I)-chelated high-loading heterogeneous catalyst (SiO2@CuI-TpBpy). SiO2@CuI-TpBpy shows high catalytic activity in three-component Huisgen 1,3-dipolar cycloaddition, giving the corresponding triazoles with excellent yields and reposeful recyclability under batch conditions. The structures of the catalysts remain steady, and the copper contents are basically unchanged after five cycles. Then, the catalysts are successfully applied for three-component heterogeneous catalysis in a one-pot continuous flow to prepare rufinamide in 89% yield for 24 h stably and efficiently with mere traces of copper ions remaining. More importantly, the catalytic system reveals a minuscule effect of catalyst particle size on internal diffusion. This COF encapsulation strategy presents a new possibility for the design of industrial heterogeneous catalysts with high metal loading and low internal diffusion resistance.

Continuous flow catalysis with CuBTC improves reaction time for synthesis of xanthene derivatives.

The copper-based metal-organic framework (MOF) CuBTC (where H3BTC = benzene-1,3,5-tricarboxylate) has been shown to be an efficient heterogeneous catalyst for the generation of 1,8-dioxo-octa-hydro xanthene derivatives, which are valuable synthetic targets for the pharmaceutical industry. We have applied this catalytic capability of CuBTC to a continuous flow system to produce the open chain form of 3,3,6,6-tetramethyl-9-phenyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione, a xanthene derivative from benzaldehyde and dimedone. An acid work-up after producing the open chain form of the xanthene derivative was used to achieve ring closure and form the final xanthene product. The CuBTC used to catalyze the reaction under continuous flow was confirmed to be stable throughout this process via analysis by SEM, pXRD, and FT-IR spectroscopy, elemental analysis, and XPS. The reaction to produce the open-chain form of the xanthene derivative produced an average yield of 33% ± 14% under the continuous flow (compared to 33% ± 0.12% of performing it under batch conditions). Based on the data obtained from this work, the continuous flow system required 22.5x less time to produce the desired xanthene derivative at comparable yields to batch reaction conditions. These results would allow for the xanthene derivative to be produced much faster, at a lower cost, and require less personal time while also removing the need to perform catalyst remove post reaction.

Comparative Evaluation of the Asymmetric Synthesis of (S)-Norlaudanosoline in a Two-Step Biocatalytic Reaction with Whole Escherichia coli Cells in Batch and Continuous Flow Catalysis

Opioids are important analgesics, and their pharmaceutical application is increasing worldwide. Many opioids are based on benzylisoquinoline alkaloids (BIA) and are still industrially produced from Papaver somniferum (opium poppy). (S)-norlaudanosoline ((S)-NLS) is a complex BIA and an advanced intermediate for diverse pharmaceuticals. The efficient synthesis of this scaffold could pave the way for a plant-independent synthesis platform. Although a promising biocatalytic route to (S)-NLS using norcoclaurine synthase (NCS) and ω-transaminase (TAm) has already been explored, the cost-effectiveness of this process still needs much improvement. Therefore, we investigated whether the synthesis could also be performed using whole cells to avoid the use of (partially) purified enzymes. With an optimized mixing ratio of TAm- and NCS-containing cells in batch biotransformations, 50 mM substrate was converted within 3 h with more than 90% yield and a high enantiomeric excess of the product (95%). To further increase the space–time yield, the cells were immobilized to enable their retainment in fixed-bed reactors. A comparison of glass beads, Diaion HP-2MG and alginate revealed that the addition of Diaion during bacterial growth led to the most active immobilisates. To facilitate sustained production of (S)-NLS, a fixed-bed setup was constructed based on lithographically printed columns from biocompatible PRO-BLK 10 plastic. The continuous production at two scales (5 mL and 50 mL columns) revealed insufficient system stability originating from biocatalyst leaching and inactivation. Thus, while the use of whole cells in batch biotransformations represents an immediate process improvement, the transfer to flow catalysis needs further optimization.

Catalytic two-dimensional Pd decorated graphene oxide membrane for efficient 4-nitrophenol reduction

Catalytic Pd decorated graphene oxide (Pd/GO) membrane with efficient catalytic activity was developed by in-situ reduction of Pd2+ on GO nanosheets followed by vacuum filtration. A high 4-nitrophenol (4-NP) reduction efficiency was achieved by using the Pd/GO catalytic membrane with layered structure because of evenly distribution of Pd nanoparticles (NPs) in the interlayer space of GO membrane, ensuring sufficient contact between 4-NP molecules and Pd NPs. The apparent kinetic rate constant and turnover frequency (TOF) reached to 138.4 s−1 and 813 h−1 under a continuous-flow system using 4000 mg/L of 4-NP at 20 °C. During a 300 min of continuous-flow catalysis, the 4-NP conversion was kept above 98% at 20 °C. This high catalytic efficiency of the Pd/GO catalytic membrane under high 4-NP concentration and continuous-flow catalysis made it promising and competitive in the application of catalytic membrane for efficient catalytic process.

Bottom-Up Synthesis of Multicompartmentalized Microreactors for Continuous Flow Catalysis.

The bottom-up assembly of biomimetic multicompartmentalized microreactors for use in continuous flow catalysis remains a grand challenge because of the structural instability or the absence of liquid microenvironments to host biocatalysts in the existing systems. Here, we address this challenge using a strategy that combines stepwise Pickering emulsification with interface-confined cross-linking. Our strategy allows for the fabrication of robust multicompartmentalized liquid-containing microreactors (MLMs), whose interior architectures can be exquisitely tuned in a bottom-up fashion. With this strategy, enzymes and metal catalysts can be separately confined in distinct subcompartments of MLMs for processing biocatalysis or chemo-enzymatic cascade reactions. As exemplified by the enzyme-catalyzed kinetic resolution of racemic alcohols, our systems exhibit a durability of 2000 h with 99% enantioselectivity. Another Pd-enzyme-cocatalyzed dynamic kinetic resolution of amines further demonstrates the versatility and long-term operational stability of our MLMs in continuous flow cascade catalysis. This study opens up a new way to design efficient biomimetic multicompartmental microreactors for practical applications.

Peptide‐based Organocatalyst on Stage: Functionalizing Mesoporous Silica by Tetrazine‐Norbornene Ligation

AbstractOrganocatalysis via the enamine mechanism developed to one of the most relevant tools in carbonyl chemistry and is widely used in asymmetric organic synthesis. In this work, a strategy is presented to conveniently immobilize a peptide‐based catalyst on silica supports for use in continuous flow catalysis reactions. A set of different porous silica supports is investigated spanning from mesoporous silica particles with defined pore sizes suitable for packed bed column reactors to silica monoliths with hierarchical meso‐macropore spaces. While the silica supports are functionalized with norbornene entities, the peptide‐based organocatalyst is modified with a tetrazine moiety, enabling the immobilization via inverse electron‐demand Diels‐Alder (IEDDA) reaction. The ligation results in catalyst loadings up to 0.2 mmol g‐1, without compromising the mesopore network. The catalytic activity of the materials is proven by the asymmetric C−C coupling reaction of n‐butanal to ß‐nitrostyrene proceeding in high yield and enantioselectivity in both batch and continuous flow setups.

Gamma-ray assisted synthesis of silver nanoparticles to improve advanced oxidation process for continuous flow catalysis and environmental remediation

Gamma-ray assisted synthesis of silver nanoparticles to improve advanced oxidation process for continuous flow catalysis and environmental remediation

Biosynthesis of Furfurylamines in Batch and Continuous Flow by Immobilized Amine Transaminases

Building blocks with amine functionality are crucial in the chemical industry. Biocatalytic syntheses and chemicals derived from renewable resources are increasingly desired to achieve sustainable production of these amines. As a result, renewable materials such as furfurals, especially furfurylamines like 5-(hydroxymethyl)furfurylamine (HMFA) and 2,5-di(aminomethyl)furan (DAF), are gaining increasing attention. In this study, we identified four different amine transaminases (ATAs) that catalyze the reductive amination of 5-(hydroxymethyl)furfural (HMF) and 2,5-diformylfuran (DFF). We successfully immobilized these ATAs on glutaraldehyde-functionalized amine beads using multiple binding and on amine beads by site-selective binding of the unique Cα-formylglycine within an aldehyde tag. All immobilized ATAs were efficiently reused in five repetitive cycles of reductive amination of HMF with alanine as co-substrate, while the ATA from Silicibacter pomeroyi (ATA-Spo) also exhibited high stability for reuse when isopropylamine was used as an amine donor. Additionally, immobilized ATA-Spo yielded high conversion in the batch syntheses of HMFA and DAF using alanine (87% and 87%, respectively) or isopropylamine (99% and 98%, respectively) as amine donors. We further demonstrated that ATA-Spo was effective for the reductive amination of HMF with alanine or isopropylamine in continuous-flow catalysis with high conversion up to 12 days (48% and 41%, respectively).

Limonene carbonate synthesis from CO2: Continuous high-pressure flow catalysis with integrated product separation

In this work, a proof-of-concept of a continuous flow process for the synthesis of limonene carbonate (LC) from the cycloaddition reaction between CO2 and limonene oxide (LO) was explored. The process uses a biphasic system composed of a CO2 mobile-phase and a stationary ionic liquid (IL)-phase used as the reaction catalyst. To determine the best conditions for integrating reaction and separation steps, high-pressure phase behaviour studies of the binary mixtures CO2 +LO and CO2 +LC were performed. The continuous process was carried out at a pressure of 300 bar and temperatures of 100 ºC, 120 ºC and 140 ºC, using two different ILs as catalysts, namely tetrabutylammonium bromide (TBABr) and trioctylmethylammonium chloride (Aliquat Cl). Results showed that at lower temperature conditions it was possible to continuously carry out the reaction for 45 h with moderate yields. TBABr revealed to be a more stable catalytic phase when compared with Aliquat Cl.

Co‐compartmentalization of Enzymes and Cofactors within Pickering Emulsion Droplets for Continuous‐Flow Catalysis

AbstractCo‐immobilization of enzymes and cofactors in a manner suitable for use in continuous flow catalysis remains a great challenge because of the difficulty in ensuring the free accessibility of immobilized enzymes and cofactors. Herein, we present a continuous flow catalysis system based on co‐compartmentalization of enzymes and cofactors within Pickering emulsion droplets, enabling regeneration of cofactors within the droplets. As exemplified by enzyme‐catalyzed ketone enantioselective reduction and enantioselective transamination, our systems exhibit long‐term stability (300–400 h), outstanding total turnover number (TTN, 59204 mol mol−1) and several‐fold enhancement in the enzyme catalytic efficiency (CEe) in comparison to conventional biphasic reactions. As well as giving insight into the co‐compartmentalization effects, our system will provide the opportunity to significantly advance continuous‐flow biocatalysis towards the level of practical applications.

Co-compartmentalization of Enzymes and Cofactors within Pickering Emulsion Droplets for Continuous-Flow Catalysis.

Co-immobilization of enzymes and cofactors in a manner suitable for use in continuous flow catalysis remains a great challenge because of the difficulty in ensuring the free accessibility of immobilized enzymes and cofactors. Herein, we present a continuous flow catalysis system based on co-compartmentalization of enzymes and cofactors within Pickering emulsion droplets, enabling regeneration of cofactors within the droplets. As exemplified by enzyme-catalyzed ketone enantioselective reduction and enantioselective transamination, our systems exhibit long-term stability (300-400 h), outstanding total turnover number (TTN, 59204 mol mol-1 ) and several-fold enhancement in the enzyme catalytic efficiency (CEe ) in comparison to conventional biphasic reactions. As well as giving insight into the co-compartmentalization effects, our system will provide the opportunity to significantly advance continuous-flow biocatalysis towards the level of practical applications.

Perpetual hyperpolarization of allyl acetate from parahydrogen and continuous flow heterogeneous hydrogenation with recycling of unreacted propargyl acetate

A novel closed loop, continuous flow (CF) reactor system for parahydrogen enhanced nuclear magnetic resonance (NMR) of liquids via heterogeneous catalysis is introduced which enables recycling of unreacted liquid substrate reactant. This system consists of an HPLC pump, a liquid substrate reservoir incorporating a gas diffuser, an all-metal packed bed catalytic reactor, and an AF-2400 tube-in-tube gas permeable membrane for removal of normal H2. Two types of supported metal nanoparticle catalysts were tested: mesoporous silica encapsulated Pt3Sn intermetallic nanoparticles and a Rh on anatase TiO2 support. In the CF hydrogenation of propargyl acetate to allyl acetate, the hyperpolarized signals exhibited stability over 20 min of recirculation, with signal enhancements of up to 626 using 99% p-H2 and negligible leaching of the catalyst into the flowing solutions. These results demonstrate the practicality of performing systematic optimization of conditions for continuous flow catalysis and polarization transfer to heteronuclei with important implications for biomedical magnetic resonance imaging.

Pickering Emulsion Catalysis: Interfacial Chemistry, Catalyst Design, Challenges, and Perspectives

AbstractPickering emulsions are particle‐stabilized surfactant‐free dispersions composed of two immiscible liquid phases, and emerge as attractive catalysis platform to surpass traditional technique barrier in some cases. In this review, we have comprehensively summarized the development and the catalysis applications of Pickering emulsions since the pioneering work in 2010. The explicit mechanism for Pickering emulsions will be initially discussed and clarified. Then, summarization is given to the design strategy of amphiphilic emulsion catalysts in two categories of intrinsic and extrinsic amphiphilicity. The progress of the unconventional catalytic reactions in Pickering emulsion is further described, especially for the polarity/solubility difference‐driven phase segregation, “smart” emulsion reaction system, continuous flow catalysis, and Pickering interfacial biocatalysis. Challenges and future trends for the development of Pickering emulsion catalysis are finally outlined.

Application of multi-wall carbon nanotubes supported l-proline in continuous flow catalysis

l-proline on multi-wall carbon nanotubes (l-proline/MWCNTs) catalysts doped with suitable auxiliary support materials are successfully applied in the continuous flow catalytic syntheses, including Aldol reaction, Mannich reaction and Knoevenagel condensation reaction. With the advantages of easy operation, high efficiency and excellent stability, this method is promising in large-scale synthesis.

Turning Electronic Waste to Continuous-Flow Reactor Using Porous Aromatic Frameworks.

Extraction of valuable metals such as gold from electronic wastes (e-waste) is regarded as a promising way of environmental remediation; however, this process is still confronted with the cost-ineffective product for normal usages like electronic devices or jewelry. Therefore, there would be merits in directly converting gold from e-waste to materials of higher value, for example, catalysts for pollutant treatment. Herein, a porous aromatic framework (PAF) with cationic sites, named iPAF-7, was synthesized and exhibited rapid extraction of gold from e-waste. Au@iPAF-7 completely converted nitroarenes to arylamines within 10 s at a rate constant of 7.8 × 10-2 s-1, which is much higher than that of any other gold nanoparticle (AuNP) catalysts with solid supports reported so far. Furthermore, considering the limitations and difficulties of operating powder materials, the aerogel monolith incorporating iPAF-7 was successfully fabricated, which retained the excellent gold extraction ability and catalytic activity of its powder form, thus exhibiting its potential application for continuous-flow catalysis of nitroarene reduction.