Showing papers in "Reaction Chemistry and Engineering in 2017"
TL;DR: In this article, the energy balance and kinetic parameters describe the heat production potential and, together with heat transfer capability, the temperature development in a continuous flow reactor, and checklists for laboratory safety and risk assessment are the basis for improved laboratory work as well as for equipmentrelated safety discussions.
Abstract: Improved safety is one of the main drivers for microreactor application in chemical process development and small-scale production. Typical examples of hazardous chemistry are presented indicating potential risks also in miniaturized equipment. Energy balance and kinetic parameters describe the heat production potential and, together with heat transfer capability, the temperature development in a continuous flow reactor. Besides these calculation procedures, checklists for laboratory safety and risk assessment are the basis for improved laboratory work as well as for equipment-related safety discussions. For complete and larger chemical plants, hazard and operation (HAZOP) studies are the appropriate method of handling hazardous processes and their scale-up.
158 citations
TL;DR: In this article, the authors describe their efforts to develop electrochemical reactors for H2O2 generation with high Faradaic efficiencies of >90%, requiring cell voltages of only ∼1.6 V.
Abstract: The development of small-scale, decentralized reactors for H2O2 production that can couple to renewable energy sources would be of great benefit, particularly for water purification in the developing world. Herein, we describe our efforts to develop electrochemical reactors for H2O2 generation with high Faradaic efficiencies of >90%, requiring cell voltages of only ∼1.6 V. The reactor employs a carbon-based catalyst that demonstrates excellent performance for H2O2 production under alkaline conditions, as demonstrated by fundamental studies involving rotating-ring disk electrode methods. The low-cost, membrane-free reactor design represents a step towards a continuous, modular-scale, de-centralized production of H2O2.
150 citations
TL;DR: In this paper, a review of recent research progress in the areas of microfluidics, flow chemistry, micro total analysis, and microreaction engineering is presented, showing good prospects in research and industrial application.
Abstract: Microflow reaction is important for the miniaturization of chemical devices and systems. From an engineering perspective, excellent characteristics, including narrow residence time distribution, rapid reactant mixing, fast mass and heat transfer, and effective droplet morphology control, of segmented liquid–liquid flow in microspace are summarized in this review based on recent research progress in the areas of microfluidics, flow chemistry, micro total analysis, and microreaction engineering. Via engineering, important roles of segmented liquid–liquid flow, such as improvements in production yield, inline purification of intermediates and products, creative droplet reactors, and preparation of particle materials with various structures, are introduced. The scale-up of micro devices and large-scale production of chemicals through microflow technology are also discussed, showing good prospects in research and industrial application.
84 citations
TL;DR: In this article, a continuous flow chemistry halogenation involving X2 and HX can be performed in a safe and controllable manner, using continuous flow flow chemistry (CFL).
Abstract: The halogenation of organic substrates is one the most important transformations in organic synthesis. The most straightforward, inexpensive and atom economic halogenations involve the use of elemental halogens (X2) or hydrogen halides (HX). However, X2 and HX reagents are highly reactive, toxic and corrosive materials. Halogenations using these reagents are usually very fast and exothermic reactions, in which selectivity issues occur. Using continuous flow chemistry halogenations involving X2 and HX can be performed in a safe and controllable manner. Reagents can be accurately dosed even for gas/liquid reactions, and exotherms are easily controlled. Hazardous chemicals can be readily quenched in line avoiding any undesired exposures and significantly enhancing the process safety.
80 citations
TL;DR: In this paper, the authors describe a novel continuous flow reactor concept for organic synthesis using heterogeneous catalysts, which is based on static mixers coated with a catalytic metal layer, which can be inserted into standard stainless steel reactor tubing.
Abstract: This work describes a novel continuous flow reactor concept for organic synthesis using heterogeneous catalysts. The concept is based on static mixers coated with a catalytic metal layer, which can be inserted into standard stainless steel reactor tubing. The static mixers were prepared by 3D metal printing, allowing for maximum design flexibility and thus can be tailored to a large number of chemical synthesis applications. The nickel or platinum catalysts were deposited either by metal cold spraying or electrodeposition, which allows for potential scale up and mass production and these techniques are compatible with a range of different catalytic metals. The catalytic flow reactor was evaluated for a series of continuous flow hydrogenations of alkenes and carbonyls.
78 citations
TL;DR: In this paper, a continuous flow reactor printed from stainless steel by selective laser melting was designed for a fast difluoromethylation reaction with nBuLi as base and fluoroform as atom-economic and inexpensive reagent.
Abstract: Herein we present a continuous flow reactor printed from stainless steel by selective laser melting. The reactor was specifically designed for a fast difluoromethylation reaction with nBuLi as base and fluoroform as atom-economic and inexpensive reagent. The reactor features four inlets to allow introduction of substrate, nBuLi, fluoroform, and a final quench solution. The reaction was completed within less than 2 min at −65 °C. The utilization of stainless steel as reactor material is critical to accomplish the heat transfer as well as the chemical and mechanical resistance that is required for this transformation.
64 citations
TL;DR: SNAr reaction profiles were generated using an automated reactor, collected in less than 3 hours, and allowed accurate estimation of kinetic parameters.
Abstract: Today, the generation of kinetic models is still seen as a resource intensive and specialised activity. We report an efficient method of generating reaction profiles from transient flows using a state-of-the-art continuous-flow platform. Experimental data for multistep aromatic nucleophilic substitution reactions are collected from an automated linear gradient flow ramp with online HPLC at the reactor outlet. Using this approach, we generated 16 profiles, at 3 different inlet concentrations and 4 temperatures, in less than 3 hours run time. The kinetic parameters, 4 rate constants and 4 activation energies were fitted with less than 4% uncertainty. We derived an expression for the error in the observed rate constants due to dispersion and showed that such error is 5% or lower. The large range of operational conditions prevented the need to isolate individual reaction steps. Our approach enables early identification of the sensitivity of product quality to parameter changes and early use of unit operation models to identify optimal process-equipment combinations in silico, greatly reducing scale up risks.
63 citations
TL;DR: In this article, the design and manufacturing of miniaturised continuous flow oscillatory baffled reactors (mCOBR) employing low cost stereolithography based 3D printing is reported for the first time.
Abstract: The implementation of advanced reactor engineering concepts employing additive manufacturing is demonstrated. The design and manufacturing of miniaturised continuous flow oscillatory baffled reactors (mCOBR) employing low cost stereolithography based 3D printing is reported for the first time. Residence time distribution experiments have been employed to demonstrate that these small scale reactors offer improved mixing conditions at a millimetre scale, when compared to tubular reactors. Nearly monodisperse silver nanoparticles have been synthesised employing mCOBR, showing higher temporal stability and superior control over particle size distribution than tubular flow reactors.
59 citations
TL;DR: In this article, the authors demonstrate that decreasing the helix diameter of the reactor promotes the onset of transversal flows and radial mixing in helical reactors, which enable fast nucleation and homogeneous growth during the synthesis.
Abstract: This paper demonstrates the critical effect of the curvature of microreactors on the size distribution of silver nanoparticles during their continuous synthesis in the absence of capping ligands. By a combination of experimental data and deep understanding of the fluid dynamics inside the reactor, we demonstrate that decreasing the helix diameter of the reactor promotes the onset of transversal flows and radial mixing in helical reactors. These secondary flows enable fast nucleation and homogeneous growth during the synthesis leading to a delicate control of the particle size distribution. A similar effect is achieved by increasing the total flow rate, assuming that the Dean number is above ∼5, while no effect of the pitch distance within the experimental range on the size distribution is observed. These results will directly impact the nanomaterial field and the development of manufacturing routes as the size of the nanoparticles is known to play a key role in determining their chemical and physical properties.
55 citations
TL;DR: In this article, the initial breakdown kinetics of cellulose were examined from 385 °C to 505 °C using a millisecond, thin-film reactor called PHASR (pulse-heated analysis of solid/surface reactions).
Abstract: Thermochemical conversion of lignocellulosic materials for production of biofuels and renewable chemicals utilizes high temperature to thermally decompose long-chain cellulose to volatile organic compounds. Cellulose undergoes two distinct kinetic regimes of intra-chain scission: low-temperature glycosidic bond cleavage (T 467 °C) associated with a high apparent activation energy. In this work, the initial breakdown kinetics of cellulose were examined from 385 °C to 505 °C using a millisecond, thin-film reactor called PHASR (pulse-heated analysis of solid/surface reactions). Using the cellulose surrogate, α-cyclodextrin, the energetics of each kinetic regime were characterized by measuring the conversion between 20 ms and 2.0 seconds. The low temperature kinetic regime exhibited glycosidic bond cleavage (Ea,1 = 23.2 ± 1.9 kcal mol−1, k0,1 = 2.0 × 107 s−1), while the high temperature kinetic regime (Ea,2 = 53.7 ± 1.1 kcal mol−1, k0,2 = 2.4 × 1016 s−1) was consistent with four reaction mechanisms including concerted transglycosylation. Apparent energetics were compared with computed literature values.
53 citations
TL;DR: In this paper, the effect of zeolite topology on the structural and kinetic changes that occur to Cu-zeolites used in NOx abatement was studied.
Abstract: Three small-pore, eight-membered ring (8-MR) zeolites of different cage-based topology (CHA, AEI, RTH), in their proton- and copper-exchanged forms, were first exposed to high temperature hydrothermal aging treatments (1073 K, 16 h, 10% (v/v) H2O) and then to reaction conditions for low temperature (473 K) standard selective catalytic reduction (SCR) of NOx with ammonia, in order to study the effect of zeolite topology on the structural and kinetic changes that occur to Cu-zeolites used in NOx abatement. UV-visible spectra were collected to monitor changes to Cu structure and showed that band intensities for isolated, hydrated Cu2+ cations (∼12 500 cm−1) remain constant after hydrothermal aging, but decrease in intensity upon subsequent exposure to low temperature SCR reaction conditions. Standard SCR rates (per Cu, 473 K), activation energies, and reaction orders are similar between Cu-AEI and Cu-CHA zeolites before and after hydrothermal aging, although rates are lower after hydrothermal aging as expected from the decreases in intensity of UV-visible bands for Cu2+ active sites. For Cu-RTH, rates are lower (by 2–3×) and apparent activation energies are lower (by ∼2×) than for Cu-AEI or Cu-CHA. These findings suggest that the RTH framework imposes internal transport restrictions, effectively functioning as a one-dimensional framework during SCR catalysis. Hydrothermal aging of Cu-RTH results in complete deactivation and undetectable SCR rates, despite X-ray diffraction patterns and Ar micropore volumes (87 K) that remain unchanged after hydrothermal aging treatments and subsequent SCR exposure. These findings highlight some of the differences in low temperature SCR behavior among small-pore Cu-zeolites of different topology, and the beneficial properties conferred by double six-membered ring (D6R) composite building units. They demonstrate that deleterious structural changes to Cu sites occur after exposure to hydrothermal aging conditions and SCR reactants at low temperatures, likely reflecting the formation of inactive copper-aluminate domains. Therefore, the viability of Cu-zeolites for practical low temperature NOx SCR catalysis cannot be inferred solely from assessments of framework structural integrity after hydrothermal aging treatments, but also require Cu active site and kinetic characterization after hydrothermally aged zeolites are exposed to low temperature SCR reaction conditions.
TL;DR: An automated reaction monitoring system capable of unattended sample aliquoting and dilution, as well as immediate quantification and identification of reaction components via HPLC-MS has been developed.
Abstract: An automated reaction monitoring system capable of unattended sample aliquoting and dilution, as well as immediate quantification and identification of reaction components via HPLC-MS has been developed. The device allows for facile reaction progress analysis, enabling mechanistic studies and serving as a primary process analytical technology (PAT) for reaction monitoring. The sampling sequence utilizes in line mixing to provide highly reproducible and accurate reaction profiles. To demonstrate the flexibility and robustness of this tool, progress curves have been acquired for three distinct reactions; namely a Cu(I)-catalysed azide-alkyne cycloaddition which is difficult to quench due to very high catalyst activity, a Suzuki cross-coupling reaction that proves challenging to monitor due to heterogenous reagents, and a complex multicomponent cascade reaction that generates multiple regioisomers that are difficult to quantify by online spectroscopic methods.
TL;DR: In this article, the robustness of a numbered-up capillary photomicroreactor system is tested when subjected to potential disturbances, such as channel blockage and light source failure.
Abstract: Limitations with regard to the scalability of photochemical reactions can be efficiently overcome by using numbered-up microreactor technology. Here, the robustness of such a numbered-up capillary photomicroreactor system is tested when subjected to potential disturbances, such as channel blockage and light source failure. Channel blockage leads to relatively large changes in both flow distribution and yield. However, we found that the performance can be accurately predicted thus making it possible to adjust the reaction parameters to obtain certain output targets. Light source failure did not lead to large variations in the mass flow distribution, highlighting the importance of the flow distributor section. Since the reaction is photocatalyzed, the impact on the reaction yield was significant in the reactor where the light failure occurred.
TL;DR: In this paper, a continuous microfluidic setup was developed to study colloidal synthesis of gold nanoparticles using tetrachloroauric acid as precursor, sodium borohydride as reducing agent and PVP as stabilizer.
Abstract: A continuous microfluidic setup was developed to study colloidal synthesis of gold nanoparticles using tetrachloroauric acid as precursor, sodium borohydride as reducing agent and PVP as stabilizer. The setup consists of pressurized vessels that allow pulsation-free flow of reactants and a microfluidic chip with integrated micromixers essential for efficient mixing with small mixing time (2 ms) followed by a meandering microchannel. The microfluidic chip enables recording X-ray absorption spectra (XAS) in situ at different positions along the microchannel at high flow rates approaching turbulent mixing conditions and thus to correlate reaction time with changes in the nanoparticle structure. Significant contributions of oxidized gold could be observed after the first 6 ms of the reaction, whereas after 10 ms principally all gold appeared to be in a metallic state. The nanoparticles obtained were characterized ex situ by various complementary techniques. The resulting nanoparticles had average diameter of 1.0 nm and narrow size distributions compared with those produced in a batch reactor. Depositing the nanoparticles on TiO2 resulted in catalysts with two different Au loadings (0.7 and 1.7 wt% Au/TiO2) which exhibited good CO oxidation activity.
TL;DR: In this article, a thermodynamic equilibrium mathematical model for a multicomponent thermodynamic vapour-liquid equilibrium model based on CH3OH as the educt and source of H2CO for OME synthesis is presented.
Abstract: Polyoxymethylene dimethyl ethers (denoted hereon as OME) are potential sustainable fuels (e.g. as a diesel substitute). In this paper, the fundamental analysis of a potentially, sustainable synthetic OME system is presented (i.e. based on CH3OH synthesised from H2 and recycled CO2). In this context, a multicomponent thermodynamic vapour–liquid equilibrium model, based on CH3OH as the educt and source of H2CO for OME synthesis, is described. A thermodynamic equilibrium mathematical model for this complex (i.e. a 29 reaction network) CH3OH–H2CO equilibrium system is presented, capable of solving the sequential chemical and phase equilibrium, importantly considering all components in the reaction system including poly(oxymethylene) hemiformals and poly(oxymethylene) glycols. A theoretical efficiency evaluation indicates that the proposed anhydrous route is potentially more attractive than the conventional synthesis (i.e. based on dimethoxymethane and trioxane). To substantiate these theoretical investigations, a complimentary experimental batch OME synthesis is also presented, providing validation for the presented thermodynamic model. An initial kinetic analysis of the OME synthesis over different commercial catalysts is also highlighted. Our presented findings reliably describe the synthesis equilibrium with respect to our experimentally obtained results. The presented work supports further an operating OME synthesis framework based on CH3OH and H2CO and highlights the requirement for innovative process design regarding feed preparation, reactor technology, and product separation/fractions recycling.
TL;DR: In this article, an integrated strategy for the production of ethanol from lignocellulosic biomass is developed, where cellulose and hemicellulose fractions are first hydrolyzed into sugars using a mixture of γ-valerolactone (GVL), water, and toluene as a solvent containing dilute sulfuric acid as a catalyst, and the sugars are then co-fermented into ethanol over engineered yeast strains.
Abstract: We develop an integrated strategy for the production of ethanol from lignocellulosic biomass. Cellulose and hemicellulose fractions are first hydrolyzed into sugars using a mixture of γ-valerolactone (GVL), water, and toluene as a solvent containing dilute sulfuric acid as a catalyst, and the sugars are then co-fermented into ethanol over engineered yeast strains. Separation subsystems are designed to effectively recover GVL and toluene for reuse in biomass hydrolysis and to recover lignin and humins for heat and power generation. We also develop an alternative process, in which we recover sugars and GVL from the residual biomass. To minimize utility requirements, we conduct heat integration, which allows us to meet all heating requirements using biomass residues. Finally, we perform a range of system-level analyses to identify the major cost and technological drivers. The proposed strategy is shown to be cost-competitive with other strategies.
TL;DR: In this paper, an online monitoring of aromatic hydrocarbon production via two-step CaO-catalysed pyrolysis of poly(ethylene terephthalate) (PET), employing tandem μ-reactor-gas chromatography/mass spectrometry (TR-GC/MS) was demonstrated.
Abstract: The present work demonstrates the online monitoring of aromatic hydrocarbon production via two-step CaO catalysed pyrolysis of poly(ethylene terephthalate) (PET), employing tandem μ-reactor-gas chromatography/mass spectrometry (TR-GC/MS). PET produces high-boiling terephthalic acid (TPA) during pyrolysis, which hinders the online monitoring of PET pyrolysis. In this work, TR allowed for independent control of the PET pyrolysis and CaO catalytic reaction with a very small sample loading (<1 mg) and split injection into the GC/MS (split ratio 100 : 1) system; thus, fatal line clogging by TPA could be avoided. Thus, we successfully demonstrated the effect of CaO basicity on the time- and temperature-dependent dynamic production of aromatic hydrocarbons. Strongly basic CaO accelerated the decarboxylation of PET pyrolysates to afford useful aromatic hydrocarbons such as benzene, toluene, and styrene with 99.7% selectivity in the oil. In contrast, weakly basic CaO enhanced benzophenone production in preference to benzene formation. The poor deoxygenation ability of the weakly basic CaO increased the concentration of oxygen-containing compounds in the oil. Finally, the time- and temperature-dependent dynamic pathways and the mechanism involving strongly basic/weakly basic CaO were established. These findings allow for a clearer understanding of the nature of PET catalytic pyrolysis, which will be helpful for advancing PET recycling. Furthermore, the novel methodology—online monitoring of a two-step pyrolysis–catalytic upgrading process involving high-boiling compounds—will gain the highest demand in the fields of green chemistry and reaction engineering.
TL;DR: A successful end-to-end continuous flow synthesis of pure curcumin and two other natural derivatives present in turmeric is described.
Abstract: A successful end-to-end continuous flow synthesis of pure curcumin (1) and two other natural derivatives present in turmeric is described. Batch and continuous flow conditions were combined in order to develop the end-to-end process. Three operations were telescoped yielding the three different natural curcuminoids in a safe, gram-scale and reproducible manner.
TL;DR: In this paper, a miniaturised polypropylene reactor was fabricated by 3D printing using fused deposition modeling, and a stainless steel nanoelectrospray ionisation capillary and a magnetic stir bar were integrated into the reactor during the printing process.
Abstract: A miniaturised polypropylene reactor was fabricated by 3D printing using fused deposition modeling. A stainless steel nanoelectrospray ionisation capillary and a magnetic stir bar were integrated into the reactor during the printing process. The integrated nanoelectrospray ionisation capillary allows direct sampling of a reaction solution without external pumping. It also allows ionisation of the analytes. Therefore, very rapid online mass spectrometric chemical reaction monitoring is possible. Operation of the miniaturised reactor is shown by the online nanoelectrospray mass spectrometry characterisation of a Diels–Alder reaction and the subsequent retro Diels–Alder reaction.
TL;DR: In this paper, a Monte Carlo ray tracing algorithm was used to simulate photon paths within LSC-PMs and the simulation results were then used to investigate the expected efficiency of scaled-up devices.
Abstract: Luminescent solar concentrator-based photomicroreactors (LSC-PMs) have been recently proposed for sustainable and energy-efficient photochemical reactions. Herein, a Monte Carlo ray tracing algorithm to simulate photon paths within LSC-PMs was developed and experimentally validated. The simulation results were then used to investigate the expected efficiency of scaled-up devices. A novel metric, defined as the ‘Average Photon Path Traveled in the Device’ (APPTD), was introduced to measure the impact of different channel design choices and to rationalize the LSC-PM improvement over traditional LSC. The simulation results suggest that the combination of luminescent solar concentrators and continuous-flow photochemistry has the potential to become the most photon-efficient application of LSCs reported to date.
TL;DR: In this paper, the Knoevenagel condensation was employed with an aminopropylated silica monolith integrated into an on-line coupled, high-pressure reaction analysis system.
Abstract: Hierarchical, macro-mesoporous silica monoliths with domain sizes (sum of mean macropore size and skeleton thickness) of ∼1 μm are highly efficient supports in heterogeneous catalysis with single-phase liquid flow. Their unprecedented performance regarding low backmixing, the elimination of internal and external diffusive transport limitations, as well as the simultaneous realization of a large (internal and external) surface area of the monolith skeleton allow reactor operation under exclusive reaction control. For experimental characterization, the Knoevenagel condensation was employed with an aminopropylated silica monolith integrated into an on-line coupled, high-pressure reaction–analysis system. It allows precise, fully automated adjustment and control of all relevant reaction parameters and promises a boost in the rapid, reproducible determination of the intrinsic reaction kinetics, in general. Hydrodynamic and reaction kinetic parameters identify extreme plug-flow conditions with this high-surface-area, compact type of microreactor and quasi-homogeneous operation in continuous-flow mode.
TL;DR: In this paper, the challenge and outlook for microfluidic ring-opening polymerization were also discussed, and the authors highlighted recent progress in continuous flow ringopening polymerizations. But they did not consider the use of micro-fluidics in the manufacturing of polymers.
Abstract: Ring-opening polymerization is one of the three polymerization methodologies, together with addition polymerization and polycondensation. Poly(ester), poly(2-oxazoline), poly(phosphoester), poly(ether), poly(amino acid) and nylon 6 are mainly synthesized via ring-opening polymerizations of their corresponding cyclic monomers. To obtain well-defined and cost-effective polymers, the combination of ring-opening polymerization and microflow technology has drawn great interest from both academia and industry. This article highlighted recent progress in continuous flow ring-opening polymerizations. Lactone, lactide, 2-oxazoline and cyclic phosphate were assessed as cyclic monomers in consecutive order. The challenge and outlook for microfluidic ring-opening polymerization were also discussed.
TL;DR: In this article, the concept of process intensification applied to the extraction of essential oil (EO) was discussed and compared with those from conventional hydrodistillation (HD) using water and three mixtures of water with three different ILs synthesized ad hoc, as maceration and extraction media, and analyzed by a multivariate statistical analysis approach.
Abstract: This paper deals with the concept of process intensification applied to the extraction of essential oil (EO). Microwave hydrodistillation (MWHD) and simultaneous ultrasound MW-assisted hydrodistillation (US-MWHD) were intensified by coupling them with a green tool: ionic liquids (ILs). The yield and chemical composition of the cumin EO obtained by MWHD and US-MWHD were compared with those from conventional hydrodistillation (HD) using water and three mixtures of water with three different ILs synthesized ad hoc, as maceration and extraction media, and analysed by a multivariate statistical analysis approach. The cumin EO was chemically characterized by GC and GC-MS analysis. The interaction of the ILs and ILs–H2O mixtures with MW was experimentally investigated and discussed, while the ILs dipole moments and optimized geometry in vacuo and in water were calculated at the DFT level. The different approaches were also compared in terms of energy and time savings. All the data clearly showed that the most promising approach was US-MWHD using a 1,3-dimethylimidazolium dimethylphosphate mixture as maceration and extraction medium. A total yield increase was achieved of up to 75% and an energy saving of 46% compared to the classical HD. The proposed technology, using ILs as green solvents, which fits well with the MW and US technology, enabled a continuous-flow and batch extractor to be constructed which would be useful for industrial applications.
TL;DR: In this paper, a new approach for the green synthesis of α-amino acids using electrochemical carboxylation of imines in a flow microreactor was described, which has the major advantage of not requiring sensitive, expensive, or toxic reagents.
Abstract: A new approach for the green synthesis of α-amino acids using electrochemical carboxylation of imines in a flow microreactor is described. This method has the major advantage of not requiring sensitive, expensive, or toxic reagents. In addition, the reaction could be conducted using single flow-through operations, without the need for sacrificial anodes and under very mild and green conditions. Our microreactor system enabled the electrochemical synthesis of N-phenylphenylglycine derivatives in good to moderate yields.
TL;DR: In this article, the batch-to-flow translation of inter-and intramolecular strategies for the diastereoselective preparation of the active pharmaceutical ingredient threo-methylphenidate hydrochloride is presented.
Abstract: The batch-to-flow translation of inter- and intramolecular strategies for the diastereoselective preparation of the active pharmaceutical ingredient threo-methylphenidate hydrochloride is presented. Both inter- and intramolecular strategies imply the telescoping of multiple processing steps and the generation of unstable diazo species under continuous-flow conditions. The intermolecular strategy relies on an unprecedented continuous-flow Rh-catalyzed intermolecular C–H carbene insertion, providing enriched threo-N-Boc methylphenidate in 38% or 19% isolated yield according to sequential or fully telescoped processes, respectively. Quantitative Boc-deprotection is carried out off-line. The intramolecular strategy relies on a continuous-flow thermal intramolecular C–H carbene insertion, providing enriched threo-methylphenidate hydrochloride in 70% isolated yield. A continuous-flow photochemical alternative is also presented. The critical step of the most promising intramolecular strategy is implemented on the mesoscale in a pilot-scale continuous-flow reactor.
TL;DR: In this article, non-reactive and reactive heat transfer experiments were performed in the FlowPlate® system manufactured by Ehrfeld Mikrotechnik, which is composed of alternating reactor and heat transfer fluid plates within a rack.
Abstract: Non-reactive and reactive heat transfer experiments were performed in the FlowPlate® system manufactured by Ehrfeld Mikrotechnik, which is composed of alternating reactor and heat transfer fluid plates within a rack. The non-reactive model system studied a rectangular serpentine channel with Reynolds numbers ranging from 400–2000, and a Gnielinski-type model was fit to the internal Nusselt number. A silver-based thermal paste was shown to reduce the external resistance to heat transfer between the reactor and heat transfer fluid plates by ∼70%, leading to overall heat transfer coefficients of ∼2200 W m−2 K−1. In the reactive system, the synthesis of methyl 2-oxobutanoate, using dimethyl-oxalate and the Grignard reagent ethylmagnesium chloride, was highlighted as a test reaction to differentiate localized heat transfer characteristics across different reactors. The Grignard reaction was used to compare the impact of various micro-mixer geometries, materials, injection ports, and scales on hotspot formation in the reactors. Finally, an analysis of four case studies that can be extended to any micro-reactor system with known overall heat transfer coefficients was presented using the fourth Damkohler number to determine a maximum channel diameter that would remove energy sufficiently quick to avoid hotspot formation.
TL;DR: In this article, the authors describe an effective means of defining optimisation criteria for self-optimising reactors, applicable to situations where a compromise is sought between several competing objectives, in which a lead property is optimised subject to constraints on the values that other properties may assume.
Abstract: We describe an effective means of defining optimisation criteria for self-optimising reactors, applicable to situations where a compromise is sought between several competing objectives. The problem is framed as a constrained optimisation, in which a lead property is optimised subject to constraints on the values that other properties may assume. Compared to conventional methods (using weighted-sum- and weighted-product-based merit functions), the approach described here is more intuitive, easier to implement, and yields an optimised solution that more faithfully reflects user preferences. The method is applied here to the synthesis of o-xylenyl adducts of Buckminsterfullerene, using a cascadic reaction of the form X0 → X1 → X2 → … XN. Specifically, we selectively target the formation of the (technologically useful) first- and second-order adducts X1 and X2, while at the same time suppressing the formation of unwanted higher-order products. More generally, the approach is applicable to any chemical optimisation involving a trade-off between competing criteria. To assist with implementation we provide a self-contained software package for carrying out constrained optimisation, together with detailed tutorial-style instructions.
TL;DR: In this paper, a compact lab plant was designed for the continuous-flow synthesis of fluorine-containing compounds and was combined with an NMR analysis platform based on a benchtop NMR spectrometer.
Abstract: A compact lab plant was designed for the continuous-flow synthesis of fluorine-containing compounds and was combined with an NMR analysis platform based on a benchtop NMR spectrometer. The approach of a unified synthesis and analysis strategy for fine chemicals was applied to three different reactions, all employing fluorine as a chemical probe for online-19F NMR analysis. A high temperature synthesis for the deprotection of a CF2H group was done as well as Ruppert–Prakash reactions for the perfluoroalkylation of benzaldehyde as a model substrate. The C–H arylation of furan with a trifluoromethylated aryldiazonium salt was performed as an example of a photochemically catalyzed reaction. All three reaction classes challenge the synthesis and analysis setup differently according to sample preparation (premagnetization of bubble-free sample) and spectrometer sensitivity (signal to noise ratio, spectral resolution, scan number, substrate concentration and flow rate), but nonetheless prove the successful application of the continuous-flow synthesis of fluorinated fine chemicals with integrated online NMR analysis.
TL;DR: In this paper, the authors demonstrate the robust, nonfouling continuous synthesis of catalytically active palladium nanoparticles using a triphasic segmented flow in a hybrid milli-meso flow reactor, which not only allows to completely eliminate fouling over extended operational duration, but also allows the achievement of ∼10 L per day volumetric productivity.
Abstract: In this communication, we demonstrate the robust, non-fouling continuous synthesis of catalytically active palladium nanoparticles using a triphasic segmented flow in a hybrid milli–meso flow reactor, which not only allows us to completely eliminate fouling over extended operational duration, but also allows the achievement of ∼10 L per day volumetric productivity in a single-channel reactor. From the synthesis perspective, we select the harshest challenge for this demonstration – the aqueous flow synthesis of metal nanoparticles using the strong, gas-evolving reducing agent sodium borohydride. We also present comparative evaluations of the catalytic activities of flow-synthesized nanoparticles compared to their batch counterparts in a model hydrogenation reaction to highlight the consistency and quality of the nanoparticles produced by the scaled-up flow synthesis.
TL;DR: Redox colorimetric tests have been devised for the rapid analysis of individual components of aqueous mixtures of peroxodisulfate, peroxomonosulfate and hydrogen peroxide; providing a convenient and selective method for the determination of these industrially relevant oxidants, which are known to interconvert in solution.
Abstract: Redox colorimetric tests have been devised for the rapid analysis of the individual components of aqueous mixtures of peroxodisulfate, peroxomonosulfate and hydrogen peroxide; providing a convenient and selective method for the determination of these industrially relevant oxidants, which are known to inter-convert in solution.