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Ammonia, being the second largest produced industrial chemical, is used as a raw material for many chemicals. Besides, there is a growing interest in the applications of ammonia as electrical energy storage chemical, as fuel, and in selective catalytic reduction of NOx. These applications demand on-site distributed ammonia production under mild process conditions. In this paper, we investigated 16 different transition metal and oxide catalysts supported on γ-Al2O3 for plasma-catalytic ammonia production in a dielectric barrier discharge (DBD) reactor. This paper discusses the influence of the feed ratio (N2/H2), specific energy input, reaction temperature, metal loading, and gas flow rates on the yield and energy efficiency of ammonia production. The optimum N2/H2 feed flow ratio was either 1 or 2 depending on the catalyst – substantially above ammonia stoichiometry of 0.33. The concentration of ammonia formed was proportional to the specific energy input. Increasing the reaction temperature or decreasing gas flow rates resulted in a lower specific production due to ammonia decomposition. The most efficient catalysts were found to be 2 wt% Rh/Al2O3 among platinum-group metals and 5 wt% Ni/Al2O3 among transitional metals. With the 2 wt% Rh catalyst, 1.43 vol% ammonia was produced with an energy efficiency of 0.94 g kWh−1. The observed behaviour was explained by a combination of gas-phase and catalytic ammonia formation reactions with plasma-activated nitrogen species. Plasma catalysts provide a synergetic effect by activation of hydrogen on the surface requiring lower-energy nitrogen species.

Introduction : Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is a subtype of glutamate receptor that mediates most of the fast excitatory neurotransmission in the brain. Anti-AMPAR encephalitis is an autoimmune-mediated neurological disorder, frequently accompanied by the presence of neoplasms, comprising a spectrum of paraneoplastic syndrome. Patient concerns: A 56-year-old man was admitted for deterioration in memory and aberrant psychological behaviors, which lasted for at least 20 days Diagnosis: The patient was diagnosed as anti-AMPAR encephalitis and 4 months later, he was diagnosed with small cell lung cancer. Interventions: Once diagnosis for anti-AMPAR encephalitis was confirmed, methylprednisolone was prescribed with initial dose 500 mg/d for 14 days until the patient returned to pre-illness state. Then he was discharged with oral treatment with corticosteroids. Following the diagnosis of small cell lung cancer, he received 5 rounds of chemotherapy, including carboplatin and etoposide. Outcomes: After taken the prescription of Methylprednisolone for anti-AMPAR encephalitis, he returned to pre-illness state and was discharged. In April 21, 2017, after symptoms of respiratory system showed up, he was diagnosed with small cell lung cancer and he eventually died of respiratory failure. Conclusion: Though progress has been made in recent years in diagnosis and treatment for autoimmune encephalitis, it is challenging to diagnose due to the similarity in clinical findings with other autoimmune or infectious encephalitis. In addition, it is necessary for these patients to regularly have tumor screening, considering AMPAR antibody encephalitis is closely associated with neoplasm, and the incidence of paraneoplastic syndrome is 63% to 70%.

Plasma discharges offer a direct way to convert electrical to chemical energy and to store volatile renewable energy sources. Converting CO2 in this way can contribute to reducing the greenhouse effect, and provide additional opportunity for chemical processing, e.g., on-site or on a small scale. The CO2 hydrogenation to CO via the reverse water-gas shift reaction (RWGS) generates synthesis gas for use as feedstock to different fuels and chemicals. The RWGS reaction carried out in a Dielectric Barrier Discharge (DBD) plasma reactor benefits from operation at ambient pressure and mild temperature, as compared to the harsher conditions of conventional RWGS processing. To develop that with outlook to real-life uses, e.g., toward methanol synthesis, key performances need to be achieved; that is, i.a., a threshold CO2 conversion, a high CO selectivity at low impurity (low CH4 selectivity), and a high (H2 − CO2)/(CO + CO2) ratio (favourable for high reaction rates) as well as tolerable energy efficiency. Central plasma process parameters for this are the feed gas ratio, residence time, and uniformly distributed microdischarges. The optimisation of an individual key performance can be adverse to the other so that the process exploration is a task. This gives room to introduce new plasma operation types, and the burst mode was applied for the first time to the RWGS reaction in the present work. By this fast (millisecond) periodic switching on and off the plasma, the process temperature can be reduced as well as a better microdischarge distribution can be achieved. The residence time is not only set by the flow rate, as commonly done, but also by taking the discharge gap as an additional parameter of freedom, which also impacts the reducing distribution. As a result of relevant process conditions, at CO selectivity of 98%, 337 mmol/kWh is obtained as the energy efficiency of CO formation. Whereas the best CO2 conversion of 50% and the (H2 − CO2)/(CO + CO2) ratio of 2 were obtained at respective optimum process parameters.

This research studies a continuous process for the direct synthesis of titanium nitride nanoparticles assisted by an atmospheric pressure microplasma. Titanium tetrachloride (TiCl4) is used as precursor and nitrogen is used as reacting gas. Composition and microstructure analysis (SEM, EDX, TEM, HRTEM, XRD and XPS) of the synthesized nanoparticles reveals that nanometer-sized titanium nitride (TiN) with polycrystalline nature can be directly prepared by the studied process, and the admixture of H2 gas in plasma during synthesis process can be an effective way to reduce the oxidation of TiN nanoparticles. The influence of the dissipated power and H2 concentration on the optical emission spectra of the microplasma in the operating reactor is investigated. The characteristics gas temperature of the plasma filament is estimated from the emission averaged spectra. A hypothesized mechanism of TiN synthesis in microplasma is illustrated, and comparisons with preceding researches are carried out. Based on process analysis and experimental results, the feasibility of the upscale towards industrial level production is discussed.

The direct synthesis of NOx from N2 and O2 by non-thermal plasma at an atmospheric pressure and low temperature is presented, which is considered to be an attractive option for replacement of the Haber-Bosch process. In this study, the direct synthesis of NOx was studied by packing different catalyst support materials in a dielectric barrier discharge (DBD) reactor. The support materials and their particle sizes both had a significant effect on the concentration of NOx. This is attributed to different surface areas, relative dielectric constants and particles shapes. The nitrogen could be fixed at substantially lowered temperatures by employing non-thermal plasma-catalytic DBD reactor, which can be used as an alternative technology for low temperature synthesis. The γ-Al2O3 with smallest particles size of 250–160 μm, gave the highest concentration of NOx and the lowest specific energy consumption of all the tested materials and particle sizes. The NOx concentration of 5700 ppm was reached at the highest residence time of 0.4 s and an N2/O2 feed ratio of 1 was found to be the most optimum for NOx production. In order to intensify the NOx production in plasma, a series of metal oxide catalysts supported on γ-Al2O3 were tested in a packed DBD reactor. A 5% WO3/γ-Al2O3 catalyst increased the NOx concentration further by about 10% compared to γ-Al2O3, while oxidation catalysts such as Co3O4 and PbO provided a minor (∼5%) improvement. These data suggest that oxygen activation plays a minor role in plasma catalytic nitrogen fixation under the studied conditions with the main role ascribed to the generation of microdischarges on sharp edges of large-surface area plasma catalysts. However, when the loading of active metal oxides was increased to 10%, NO selectivity decreased, suggesting possibility of thermal oxidation of NO to NO2 through reaction with surface oxygen species.\ud \ud

The methoxycarbonylation of cyclohexene with carbon dioxide over a ruthenium catalyst was realized in a micro flow system under supercritical conditions. Instead of the toxic and flammable carbon monoxide, this process utilizes carbon dioxide, thereby avoiding issues with bulk transportation of carbon monoxide as well as eliminating the need for safety precautions associated with the use of carbon monoxide. Obtained was a 77% yield of the ester product at 180 °C, 120 bar and with a 90 min residence time, which is over five times faster than for the same reaction performed under subcritical conditions in batch. An important factor for the performance of the system was to have a sufficiently polar supercritical mixture, allowing the catalyst to dissolve well. The optimal temperature for the reaction was 180 °C, as the activity of the system dropped considerably at higher temperatures, most likely due to catalyst deactivation.

In this chapter, major green metrics are described as they have been applied to microflow continuous processes (e.g., mass intensity (MI)/process mass intensity (PMI), E‐factor, atom economy, etc.). Thereafter, life cycle assessment (LCA) and life cycle costing (LCC) analysis are reviewed in the framework of their application to evaluate microflow continuous processes. Green metrics, LCA, and LCC allow an objective quantitative measurement and decision support tool to evaluate the ecological, environmental as well as the economic impact of a chemical synthesis and process. Within the approach of green chemistry, continuous microflow processing has become a major method to achieve process intensification and engineering support. Accordingly, the specific sustainability characteristics of microflow continuous processes will be described. A comparison of microscale continuous processes and conventional macroscale processes accompanied by green metrics and LCA will be conducted. This is done in a hierarchical manner, starting from single microflow reaction optimization (both with single and bundled innovation drivers) toward combined microflow reaction separation and microflow multistep reactions. The production volume under consideration is both small (pharma) and large (fine/bulk chemical). This scenario analysis allows one to draw some generic conclusions about the environmental opportunities of continuous microflow technology and, vice versa, on the suitability of these green assessment tools. Each case scenario is for a typical, mostly experimentally validated microreactor application and illustrates the pros and cons of microflow continuous processes in the fine chemical and pharmaceutical industry. The environmental analysis is completed by a snapshot of LCC analysis for these microreactor case scenarios.

The production of NOx from air and air + O2 is investigated in a pulsed powered milli-scale gliding arc (GA) reactor, aiming at a containerized process for fertilizer production. Influence of feed mixture, flow rate, temperature, and Ar and O2 content are investigated at varying specific energy input. The findings are correlated with high-speed imaging of the GA dynamics. An O2 content of 40–48% was optimum, with an enhancement of 11% in NOx production. Addition of Ar and preheating of the feed resulted in lower NOx production. Lower flow rates produced higher NOx concentrations due to longer residence time in the GA. The volume covered by GA depends strongly on the gas flow rate, emphasizing that the gas flow rate has a major impact on the GA dynamics and the reaction kinetics. For 0.5 L/min, 1.4 vol % of NOx concentration was realized, which is promising for a containerized process plant to produce fertilizer in remote locations. © 2017 American Institute of Chemical Engineers AIChE J

Nitrogen is the most basic element responsible for the growth of living creatures on earth. Chemical nitrogen fixation process is one of the most important chemical processes, which sustains the growing global population. Wherein the life changing Haber-Bosch process comes into the picture, which produces more than 130 million tons of ammonia per year by consuming ∼1–2% of the world's total energy consumption and sustains ∼40% of the world's population. Several efforts have been invested to develop an energy efficient alternative to this not-so-environmentally-friendly process. Nitric oxide and ammonia synthesis, with plasma as an alternative energy form, have been investigated extensively over the last 100 years. This review covers the important findings in the field of plasma nitrogen fixation and critically analyzes the studies reported from 1900 to 2014.

The synthesis of adipic acid from cyclohexene and hydrogen peroxide was investigated in micro-flow packed-bed reactors. The isolated yield of adipic acid increases with increasing residence time in micro-flow packed-bed reactors. The addition of phosphoric acid cannot effectively improve the isolated yield of adipic acid though it is generally known to reduce the decomposition of H2O2. Then, different temperatures were tested along the reactor length, since the adipic acid synthesis is known to consist of 6 elementary reactions with different temperature needs. For experiments with 2-stage temperature ramping, 70 °C and 100 °C, respectively, are the optimal temperatures for the first stage and second stage reactor, which lead to 63% isolated yield of adipic acid. Furthermore, 3-stage temperature ramping improves the yield of adipic acid to 66%. Multi-injection of hydrogen peroxide at different stages does not lead to a further increase in adipic acid yield. Although high temperatures are used in this transformation, the in-line recording of temperature profiles along the flow axis shows that safe operation for this exothermic reaction can be realized in the micro-flow packed-bed reactors. Notably, the space–time yields in micro-flow packed-bed reactors are more than one order of magnitude higher than those obtained in batch reactors.

Catalytic processes are of paramount importance in the chemical industry. Homogeneous catalysts are of great interest for synthesizing fine-chemical/specialty chemical/pharmaceutical products for their advantages of high activity and selectivity. However, their separation from the product remains a challenge. Transition metals and especially platinum group metals are used extensively as catalysts. They are expensive and there are strict regulations on the permitted levels of these metals in pharmaceutical products. Therefore, their effective separation is required. Moreover, we are running short of these and many other valuable metals. This puts more emphasis on the need to separate these homogeneous metal catalysts in their active form and recycle them back to the reactor. This review aims to provide the reader with an overview of the current literature on the separation/recycling methods of homogeneous transition metal catalysts in continuous flow. These include heterogenization, scavenging, using biphasic systems and organic solvent nanofiltration. There are numerous successful demonstrations on the laboratory scale and recently also on the industrial scale.

Pressure effects on regioselectivity and yield of cycloaddition reactions have been shown to exist. Nevertheless, high pressure synthetic applications with subsequent benefits in the production of natural products are limited by the general availability of the equipment. In addition, the virtues and limitations of microflow equipment under standard conditions are well established. Herein, we apply novel-process-window (NPWs) principles, such as intensification of intrinsic kinetics of a reaction using high temperature, pressure, and concentration, on azide–alkyne cycloaddition towards synthesis of Rufinamide precursor. We applied three main activation methods (i.e., uncatalyzed batch, uncatalyzed flow, and catalyzed flow) on uncatalyzed and catalyzed azide–alkyne cycloaddition. We compare the performance of two reactors, a specialized autoclave batch reactor for high-pressure operation up to 1800 bar and a capillary flow reactor (up to 400 bar). A differentiated and comprehensive picture is given for the two reactors and the three methods of activation. Reaction speedup and consequent increases in space–time yields is achieved, while the process window for favorable operation to selectively produce Rufinamide precursor in good yields is widened. The best conditions thus determined are applied to several azide–alkyne cycloadditions to widen the scope of the presented methodology.

The environmental profile of plasma assisted methane reforming for the production of synthesis gas was researched. A miniaturized gliding arc discharge reactor was applied for the partial oxidation of methane in this study. The best operational condition regarding to the lowest CO2-eq emission was screened out. Studied were the global warming potential, the acidification potential, the eutrophication potential, the human toxicity, the NOx photochemical oxidant creation potential, and the ozone depletion potential. The electricity consumption was the main contribution to the four of these six impacts. A sensitivity research of different energy resources of electricity and electricity mix of different countries was carried out in order to decrease the emission caused by the electricity consumption. Then, the conventional steam reforming was benchmarked to the plasma reforming process, which shows that the global warming potential of the plasma reforming is comparably on the same level as the conventional reforming only in the case when the electricity is generated from renewable or clean energy. So, the environmental impact research of the plasma assisted methane reforming in lab scale shed light on its industrial application from the viewpoint of the environmental profile. In order to decrease the emissions from electricity production, it’s recommended that such plasma plant should be built close to power plants from the renewable or clean energy. The compactness of plasma plants due to their expected process intensification would facilitate such distributed approach, while conventional reforming plants are very large and need Verbund-type integration into ChemParks. Finally, another option to make the plasma reforming process more energy efficient and green is proposed which is to combine the plasma reforming unit with Solid Oxide Fuel Cells.

The alkoxycarbonylation reaction can be realized in continuous flow under supercritical conditions by utilizing CO2 as a feedstock instead of CO. Conventionally, the synthesis of the methyl propionate is achieved in the first step of the Lucite Alpha process through the hydroesterification of ethylene with methanol and carbon monoxide. In this paper, synthesis of the methyl propionate process by replacing the carbon monoxide feedstock with CO2 and using a more robust and less expensive catalyst is simulated and evaluated from the perspective of environmental influence. A life cycle assessment was done of the methyl propionate production via the supercritical process utilizing CO2 as feedstock. For all nine impact categories-AP, GWP, EP, FAETP, HTP, Land use, MAETP, ODP and CED -, the novel process was compared to the performance of the existing state-of-the-art carbon monoxide-based process, the Lucite Alpha process. An 80% impact reduction was found for both the Global Warming Potential and the Ozone Depletion Potential. The major contribution to the impact reduction stems from the change from CO to CO2 as a feedstock, since the impact from CO as feedstock is strongly negative while the impact from CO2 as feedstock is strongly positive. Yet, also the supercritical conditions themselves show a notable environmental benefit, besides providing the enabling function for the new chemistry. A remarkable effect on steam, electricity, and cooling energy is given. The higher pressure required for the supercritical CO2 process was found to have minimal effect on the electricity use for compression.

Two novel routes for the production of gasoline from pyrolysis oil (from timber pine) and biogas (from ley grass) are simulated, followed by a cradle-to-gate life-cycle assessment of the two production routes. The main aim of this work is to conduct a holistic evaluation of the proposed routes and benchmark them against the conventional route of producing gasoline from natural gas. A previously commercialized method of synthesizing gasoline involves conversion of natural gas to syngas, which is further converted to methanol, and then as a last step, the methanol is converted to gasoline. In the new proposed routes, the syngas production step is different; syngas is produced from a mixture of pyrolysis oil and biogas in the following two ways: (i) autothermal reforming of pyrolysis oil and biogas, in which there are two reactions in one reactor (ATR) and (ii) steam reforming of pyrolysis oil and catalytic partial oxidation of biogas, in which there are separated but thermally coupled reactions and reactors (CR). The other two steps to produce methanol from syngas, and gasoline from methanol, remain the same. The purpose of this simulation is to have an ex-ante comparison of the performance of the new routes against a reference, in terms of energy and sustainability. Thus, at this stage of simulations, nonrigorous, equilibrium-based models have been used for reactors, which will give the best case conversions for each step. For the conventional production route, conversion and yield data available in the literature have been used, wherever available.The results of the process design showed that the second method (separate, but thermally coupled reforming) has a carbon efficiency of 0.53, compared to the conventional route (0.48), as well as the first route (0.40). The life-cycle assessment results revealed that the newly proposed processes have a clear advantage over the conventional process in some categories, particularly the global warming potential and primary energy demand; but there are also some in which the conventional route fares better, such as the human toxicity potential and the categories related to land-use change such as biotic production potential and the groundwater resistance indicator. The results confirmed that even though using biomass such as timber pine as raw material does result in reduced greenhouse gas emissions, the activities associated with biomass, such as cultivation and harvesting, contribute to the environmental footprint, particularly the land use change categories. This gives an impetus to investigate the potential of agricultural, forest, or even food waste, which would be likely to have a substantially lower impact on the environment. Moreover, it could be seen that the source of electricity used in the process has a major impact on the environmental performance.

The segmented micro-flow extraction and separation of the adjacent elements of Co from Ni sulphate solution with Cyanex 272 is developed using a micro-scale coiled flow inverter (CFI). This is compared with the conventional batch extraction in parallel. Continuous operation of a process involving liquid-liquid extraction and then two-phase separation is achieved instantly. For the latter a micro-scale separator is used. Compared with batch extraction, the segmented micro-flow extraction process shows order-of-magnitude faster extraction times, higher extraction ability for Co, lower extraction for Ni, and then a better selectivity between Co and Ni at industrial-matching concentration. Regular columnar slugs are observed at low flow rates and found to be a Gaussian function of the flow rates. Matched in- and outlet flows indicates that extraction in micro-flow is dependent on mass transfer by molecular diffusion. Extraction efficiency is enhanced by the internal circulation flow generated within slugs. Additionally, the characteristic parameters, overall volumetric mass transfer coefficient kLα and overall mass transfer coefficient kL, are measured to determine the mass transfer performance. Compared with batch, much higher kLα of Co (0.26–0.017 s−1) and smaller of Ni (0.053–0.013 s−1) are investigated in CFI. Meanwhile, 4.5 times increasement of the kL value of Co to Ni is observed in CFI indicating the asynchronous extraction between Co and Ni.

This paper reviews recent developments on the synthesis of noble metal nanoparticles in micro and millifluidic devices and their catalytic application in organic flow synthesis. A variety of synthesis methods using microfluidics is presented for gold, silver, palladium, platinum, and copper nanoparticles, including the formation in single-phase flows and multiphase flows. In the field of organic chemistry, metal nanoparticles can be used as catalysts. This can lead to remarkably improved reaction performance in terms of minimizing the reaction time and higher yields. In this context, various applications of those metal nanoparticles as catalysts in microfluidic devices are highlighted at selected examples. As a new direction and operational window, nanocatalysts may be synthesized in situ in flow and directly utilized in an organic synthesis. This allows making use of highly active, yet instable catalyst species, which may only have a very short life of a few seconds – a type of flashed nanocatalyst organic synthesis.

EDGE denotes “Explain, Demonstrate, Guide, Enable” and comes from a concept for youth leadership development training. Biotechnical and enzymatic micro-flow reactors are a young discipline. Here the enthusiasm level mirrors its technological growth and vice versa. Rather than being a linear function, enthusiasm first goes down after sudden realization of all bottlenecks and technological shortcomings which are to overcome in a Hercules task action. However, with increasing provision of technology and security in its performance, the enthusiasm level rises again. This “valley of death” needs to be crossed to bridge to a market. The enzymatic micro-flow reactors mirror the above depicted development of their counterparts – the chemical microreactors – which is already about 20 years old. This “Déjà vu” forms a feature story which encompasses a review about enzymatic microreactors and their synthetic applications which are shown in all their facets. This compilation is structured in chapters about reactor and enzyme support technology, transport intensification, chemical intensification, process-design intensification, and finally first steps into the bio-based economy.

The synthesis of adipic acid by means of a direct oxidation of cyclohexene by hydrogen peroxide was carried out in a continuous-flow packed-bed microreactor. The reaction uses Na2WO4·2H2O as a catalyst and [CH3(n-C8H17)3N]HSO4 as a phase transfer catalyst without additional solvent. A parametric process optimization, such as glass beads size, residence time, concentration of hydrogen peroxide, addition of acid, reaction temperature, and molar ratios of reactants and catalysts, was performed. It is demonstrated that smaller glass beads result in a better yield of adipic acid and that the addition of acid plays an important role in the oxidation of cyclohexene to adipic acid. Based on the concept of Novel Process Windows, the influence of elevated temperatures is investigated.

This mini-review discusses some of the recent work on novel process windows by the Micro Flow Chemistry and Process Technology group at the Eindhoven University of Technology, and their associates. Novel process windows consist of unconventional approaches to boost chemical production, often requiring harsh reaction conditions at short to very short time-scales. These approaches are divided into six routes: the use of high temperatures, high pressures, and high concentrations (or solvent-free), new chemical transformations, explosive conditions, and process simplification and integration. Microstructured reactors, due to their inherent safety, short time-scales, and the high degree of process control, are the means that make such extreme chemistry possible.

Together with transport and chemical intensification, process-design intensification is situated under the umbrella of Novel Process Windows and heads for integrated and simplified smart-scaled (micro/meso) flow process design in a holistic picture. As a demonstration example, the direct oxidation of cyclohexene with hydrogen peroxide for adipic acid synthesis is considered. It provides an innovative alternative to the two-step industrial process currently used. It is aimed to design an energy efficient process for this novel route. For systematically and holistically analyzing the process and, in particular, its heat integration, pinch analysis is employed. With the use of the software Aspen Energy Analyzer, the available energy recovery potential is determined, and a heat exchanger network is designed that gives a minimum total annual cost. Compared with the initial heat exchanger network where energy requirements are supplied with utility streams, the improved heat exchanger network designed enables 70% saving in operating cost which enables to pay back the extra capital cost requirement in 8 months. The heat exchanger selection is also a very important design consideration. The utilization of compact heat exchangers (including microchannel-based), which have proven advantages in thermal effectiveness, safety, and reduced size, can enable further benefits in terms of total plant cost and plant complexity. The opportunity to have lower operable temperature approach gives the possibility to lower the utility requirement by 20%. For the case of temperature cross, the additional capital cost requirement can be halved. As a consequence, for operation of flow processes using micro/meso-reactors at large scale, the utility/energy support and heat exchanger selection should be taken into consideration. Such holistic thinking has not been detailed and justified so far for micro- or similar smart-scale flow reactors, to our best knowledge.

Nitrogen fixed in the form of nitrogen oxides is essential to produce fertilizers and many other chemical products, which is vital to sustain life. The performance of a milli-scale gliding arc reactor operated under atmospheric pressure has been studied for nitrogen oxides synthesis. In this work, the electrical and process parameters of the gliding arc reactor, such as frequency, pulse width, amplitude and feed ratio were investigated respectively. The experiments were performed at 1 L/min in a gliding arc discharge regime. The highest concentration of NOx was found to be ~1 % at energy consumption of 10 kWh/kg of NOx. Increase in frequency, pulse width and amplitude resulted in an increased specific energy input and NOx concentration. The feed ratio (N2/O2) affected the amount of NO and NO2 produced, which gives possibility to independently obtain the desired ratio of NO/NO2 by tuning the electrical and process parameters.

The importance of nitrogen fixation is evident in every aspect of a human being’s life -from the synthesis of vital for all organisms nutrients and, in turn, the ecosystem conservation to the production of fertilizers, plastics and many other daily usage products. However, increasing concerns about the environmental sustainability of contemporary chemical industry seem to impose, nowadays, great challenges to the industrial nitrogen fixation which is linked to immense energy consumption and burdened emissions profile. Upon these considerations, it becomes imperative to adopt a holistic approach towards the development of novel “green” process technologies for the synthesis of fixed nitrogen. A considerable effort to that direction has been made by means of plasma technology mainly at laboratory scale. Although research studies have shown promising results, little attention has been placed on conceptualizing plasma-assisted nitrogen fixation at an industrial scale and evaluating its environmental footprint. This issue is practically addressed in the present research work which focuses on the ex-ante process design of plasma-assisted nitric acid synthesis for a modular plant and the respective Life Cycle Assessment (LCA) incorporating renewable energy sources. In order to facilitate the analysis of the LCA study, a sensitivity analysis has been considered on the reaction yield, the plasma power consumption, the recycle of unreacted gas stream and the energy recovery in the plasma reactor. LCA results exhibit for the plasma-assisted nitric acid, incorporating the recycle of the tail gas and solar energy, an improvement in the Global Warming Potential of 20% as compared to the conventional production pathway.

AVOIDING THE COPPERS: A continuous-flow synthesis for the Cu(I) -catalyzed azide-alkyne cycloaddition reaction using [Cu(phenanthroline)(PPh₃)₂]NO₃ as a homogeneous catalyst is developed (up to 92 % isolated yield). Elevated temperatures allow achieving full conversions and using lower catalyst loadings. Residual copper in the triazole compound is efficiently removed via an inline extraction process, employing aqueous EDTA as a copper scavenger.

Konti-Prozesse mit mikrostrukturierten Reaktoren ermoglichen Paradigmenwechsel in der Prozessentwicklung und damit auch kurzere Entwicklungszeiten bis hin zur Produktionsanlage. Der Schlussel liegt hier in analogen Prozesszustanden in der Entwicklungskette (Numbering-up), Standardisierung (Modularitat) und Intensivierung. Das Resultat ist letztendlich eine reduzierte Apparateanzahl und -grose und eine hohere Voraussagekraft im Scale-out der Anlagen. Dies wird bislang meistens uber die Transport-Intensivierung in mikrostrukturierten Reaktoren bewirkt. Ein neuer, mehr und mehr genutzter Ansatz ist die Chemie-Intensivierung durch Einsatz harscher Chemie bei ungewohnlichen Reaktionsparametern und masgeschneiderter Reaktionsumgebung. Eine ganz neuer Ansatz besteht zudem in der Prozessdesign-Intensivierung – zum einen brauchen selektivitatsoptimierte Durchflussprozesse weniger Reinigungsaufwand, zum anderen haben mikrostrukturierte Reaktoren aufgrund ihrer kleinen Baugrose und der Moglichkeit zur internen Funktionalisierung groses Potenzial fur die Systemintegration. Beide Masnahmen verandern und vereinfachen das gesamte Prozessschema grundlegend. Der modulare Aufbau der kleinen Konti-Einheiten erlaubt eine einfache Implementation in moderne modulare Anlagenumgebungen, in denen alle Testzyklen (Labor, Pilot, Produktion) in einer Anlagenumgebung durchgefuhrt werden sollen, wie z. B. Container-Anlagen. Flow processes with microstructured reactors allow paradigm chances in process development and thus can enable a faster development time to the final production plant. They do this by exploiting similarity effects along the development chain (modularity) and intensification. The final result can be a reduction of the number and size of apparatus in the plant, and a higher predictability in the scale-out of the apparatus. So far, this was mainly achieved via transport intensification given in microstructured reactors. A new idea is chemical intensification through deliberate use of harsh chemistry at unusual reaction parameters and tailor-made reaction environment. A very new idea is the process design intensification – the reaction-maximized flow processes need less separation expenditure and the small unit size together with the high degree in functionality gives large potential for system integration. The modular nature of the small flow units allow an easy implementation to modern modular plant environments, that enable to perform all the testing cycles (lab, pilot, production) in one plant environment, e.g. container plants.

Joule heat-induced hot-spot formation sets severe limits in the operation of continuous annular electrochromatography (CAEC), a new concept for preparative separation as an analog to analytical capillary electrochromatography (CEC). This may lead to eluent flow perturbance, even to boiling, which would massively weaken separation efficiency and may even hamper the stationary phase used for separation. For reasons of system integration and high-efficiency heat transfer, micro flow heat exchangers are considered with a separate coolant flow. A 3D numerical analysis of the heat transfer of water single-phase laminar flow in a square microchannel and different arrays of micro pin-fins was carried out using COMSOL Multiphysics. Several advanced materials with low electric conductivity and at the same time with high heat conductivity were put forward to be used in the CAEC system. As essential design point, it is proposed to constitute the micro heat exchanger from two different parts of the CAEC system, namely a micro-structured pin-fins plate and a so-called conductive plate.

The synthesis of 1,4-dihydropyridines was performed in a continuous-flow microreactor. Elevated temperatures accelerated the reaction rate significantly allowing the reaction to be finished in minutes (6–11 min). Different 1,4-dihydropyridines were prepared in good to excellent isolated yields (45–88% yield). The method was amenable to the preparation of daropidine, a calcium channel blocker which is currently in clinical phase 3 trials.

Life cycle assessment (LCA) and life cycle cost analysis are two prime tools that have been used to evaluate the sustainability of novel EU projects, which investigated new strategies to improve product yields and reduce costs, while ensuring a good ecological footprint and cost efficiency. These include EU projects focussed on developing modular, compact production platforms with intensified reactors–such as the F3 Factory, COPIRIDE (combining process intensification-driven manufacture of microstructured reactors and process design regarding to industrial dimensions and environment), POLYCAT (modern polymer-based catalysts and microflow conditions as key elements of innovations in fine chemical synthesis) and SYNFLOW (Innovative Synthesis in Continuous-flow Processes for Sustainable Chemical Production). New projects such as the MAPSYN (Microwave, Acoustic and Plasma assisted SYNtheses) and BIOGO (Catalytic Partial Oxidation of Bio Gas and Reforming of Pyrolysis Oil (Bio Oil) for an Autothermal Synthesis Gas Production and Conversion into Fuels) continue this, but by using alternative energy and a biomass-based, heat-integrated process, respectively. Thus, this paper is a review of EU projects that have carried out LCA and cost analyses and used the results to aid decision-making in the context of process intensification, flow chemistry and modular plants. Copyright © 2015 Curtin University of Technology and John Wiley & Sons, Ltd.

A Supported Liquid Phase Catalyst (SLPC) coating was successfully applied for the Mizoroki–Heck reaction in micro flow. Foremost, extended on stream operation was enabled and the on stream performance stability was verified. Stable catalytic activity was achieved during two consecutive runs totaling 50 h, after an initial stabilization period. Further support for the catalytic stability was provided by the fact that no leached Pd was detected in the product. Highest obtained conversion was 94% at 230 °C and a 26 min residence time. When conversion was plotted versus residence time, the reaction was shown to fit the predictions of the kinetic model. To optimize the performance of the flow system, reaction conditions and different ligands for the catalyst were initially investigated in batch, as well as various different substrates. Ethylene glycol was found to be most effective as the solvent film, while the use of water led to degradation of the silica support.

Plasma technology has been widely applied in the ozone production, material modification, gas/water cleaning, etc. Various nanomaterials were produced by thermal plasma technology. However, the high temperature process and low uniformity products limit their application for the high value added chemicals synthesis, for example the functional materials or the temperature sensitive materials. Microplasma has attracted significant attentions from various fields owing to its unique characteristics, like the high-pressure operation, non-equilibrium chemistry, continuous-flow, microscale geometry and self-organization phenomenon. Its application on the functional nanomaterial synthesis was elaborately discussed in this review paper. Firstly, the main physical parameters were reviewed, which include the electron temperature, electron energy distribution function, electron density and the gas temperature. Then four representative microplasma configurations were categorized, and the proper selection of configuration was summarized in light of different conditions. Finally the synthesis, mechanism and application of some typical nanomaterials were introduced.

The synthesis of 1,4-dihydropyridines was performed in a continuous-flow microreactor. Elevated temperatures accelerated the reaction rate significantly allowing the reaction to be finished in minutes (6–11 min). Different 1,4-dihydropyridines were prepared in good to excellent isolated yields (45–88% yield). The method was amenable to the preparation of daropidine, a calcium channel blocker which is currently in clinical phase 3 trials.

Review: recent work on novel unconventional approaches to boost chemical production including use of high temperatures, high pressure and high concentrations; 80 refs.

Threonine aldolase (TA) from Thermotoga maritima was immobilized on an Eupergit support by both a direct and an indirect method. The incubation time for the direct immobilization method was optimized for the highest amount of enzyme on the support. By introducing the immobilized TA in a packed-bed microreactor, a flow synthesis of phenylserine was developed, and the effects of temperature and residence time were studied in particular. Calculations of the Damköhler number revealed that no mass transfer limitations are given in the micro-interstices of the packed bed. The yield does not exceed 40% and can be rationalized by the natural equilibrium as well as product inhibition which was experimentally proven. The flow synthesis with the immobilized enzyme was compared with the corresponding transformation conducted with the free enzyme. The product yield was further improved by operating under slug flow conditions which is related to the very short residence time distribution. In all cases 20% diastereomeric excess (de) and 99% enantiomeric excess (ee) were observed. A continuous run of the reactant solution was carried out for 10 hours in order to check enzyme stability at higher temperature. Stable operation was achieved at 20 minute residence time. Finally, the productivity of the reactor was calculated, extrapolated to parallel run units, and compared with data collected previously.

The application of a supported aqueous phase catalyst (SAPC) coating was investigated for the Mizoroki–Heck reaction in micro flow and favorably compared to the use of an SAPC in a batch system. In batch, an 83% yield was observed after 4 h at 180 °C with a catalyst loading of 0.4 mol %, while in flow a residence time of 2.9 min provided a 21% yield with only 0.01 mol % catalyst loading. In batch the SAPC could be re-used twice without any significant loss in yield, but further re-use was prevented due to problematic accumulation of an ammonium salt. In the micro flow system, this problem could be overcome by adding water to the product flow prior to cooling, allowing even more effective use of the catalyst.

A check on environmental sustainability of microreaction technology is given based on a new process idea as a study case, which is the direct synthesis of adipic acid (ADA) in a continuous flow process using a milli-packed bed reactor with micro-sized fluid interstices. Main aim is to determine impactful process parameters and to have a holistic idea of the environmental profile for this new process by means of life cycle assessment. Second main aim is to benchmark the flow process against conventional technology to produce ADA which takes place in two steps. Whereas the conventional process for ADA synthesis occurs in two steps from oxidation of cyclohexane by air followed by nitration oxidation, the direct route is from cyclohexene and uses hydrogen peroxide as oxidant. This results in higher ADA yield and simplified process with one step less. Drawbacks of the direct synthesis are long reaction time and increased safety issues, which can be overcome by using microreactors. The reaction rate is increased by the largely improved mass transfer and the use of higher temperature. Life cycle assessment (LCA) shows that for a number of impact categories the direct process is greener; yet there are also categories for which the conventional route is more environmentally sustainable. The results, analyzed from cradle to factory gate, shed some light on the truth and comprehensiveness of the statement frequently found in the literature, that H2O2 is a green oxidant because of atom economy and non-toxicity of water produced (Noyori et al., 2003; Grigoropoulo et al., 2003; Usui and Sato, 2003; Podgorsek et al., 2009; Edwards et al., 2005; Tse et al., 2005) [1] , [2] , [3] , [4] , [5] , [6] . Further, cooling energy plays also an important role for the environmental profile. In this way, fast decisions and recommendations for process variants in the newly designed route can be given and lead to a more focused research plan which is exemplified at the end of the paper.

The MAPSYN project of the European Union (standing for Microwave, Acoustic and Plasma SYNtheses) aims at the utilization of plasma technology for nitrogen fixation reactions on an industrial scale and with industrial plasma reactor technology, developed and utilised commercially [1]. Key motif is enhanced energy efficiency to make an industrial plasma process viable for chemical industry. The corresponding enabling technologies – plasma catalysis, smart reactors (microreactors) and more – go beyond prior approaches. Continuing a first more project-based literature compilation, this overview focus on the two first enabling functions, plasma catalysis and smart reactor technology, which are reviewed for industrial and near-industrial plasma-based applications. It is thereby evident that notable promise is given for the nitrogen fixation as well and indeed this has been demonstrated also for nitrogen fixation; yet, initially and without the holistic system engineering dimension.

Novel Process Windows make use of process conditions that are far from conventional practices. This involves the use of high temperatures, high pressures, high concentrations (solvent-free), new chemical transformations, explosive conditions, and process simplification and integration to boost synthetic chemistry on both the laboratory and production scale. Such harsh reaction conditions can be safely reached in microstructured reactors due to their excellent transport intensification properties. This Review discusses the different routes towards Novel Process Windows and provides several examples for each route grouped into different classes of chemical and process-design intensification.

Recently, much focus has been given to a new type of chemical production plant, with the aim of a much faster time-to-market (“50% idea”) and better cash-flow revenue. The main enabling technology is to have the plants pre-manufactured and assembled by a modular construction and to use innovative, smart-scale processing and apparatus technology, in order to achieve a compact overall plant footprint. Focal points in such technology are on the one hand, flow processing, with micro process technology as a cutting-edge cornerstone, and on the other hand, the container framework. Yet, other process-intensified technologies are suitable as well such as milli-flow or upgraded batch technologies. Finally, process robustness and short-time applicability make the decision. In this paper, for the first time, a CAPEX and OPEX analysis of the new plant technology is done, at the example of the Evotrainer production platform. This platform is pre-manufactured in serial and provides all the utilities needed around the reactor and e.g., separator to be tailored and inserted. The unit-operational modularization, with respective definition of interfaces, was developed further to a so-called functional modularization, where different cabinets with pre-defined functions and equipment are proposed. Three virtual microreactor applications were used and stand as model-based scenarios for market applications in bulk chemistry, fine chemistry and pharmacy. It is shown, in many facets, that the Evotrainer infrastructure based plants indeed have a faster payback and higher earnings as compared to conventional technology, particularly when serving high-priced markets such as pharmaceutical applications. Further, the combination with novel chemical routes or novel processing (Novel Process Windows) is advantageous. Micro process technology is one of the key enablers and was taken here, since the dataset of such technology was readily available to the authors due to past research efforts and there is some general belief in the combination to the so-called “Future Factories”. Yet, it stands also for any other process intensification technology which can achieve the same performance level and which is able to satisfy the needs of a producing industry.

This paper consists of two parts – a detailed experimental investigation on the activity of supported threonine aldolase for use in a microreactor/flow reactor and a generic, explorative outline on potential productivity of enzymatic microreactors; with the need to use data from other enzymes here as well. Threonine aldolase was immobilized on different supports foreseen to be coated or packed within the micro- and millichannels of flow reactors. As enzyme supports, an innovative high-surface area and high-porosity silica (Nanosprings), the commercial Eupergit CM, and polymer membrane materials were used. For Eupergit CM, the share of chemically fixed enzymes and active enzymes were within the reported literature performance for enzyme immobilization. The values of immobilized enzymes on Nanosprings were somewhat lower. However, this is overcompensated by the larger specific surface area of Nanosprings and the availability of a new, second generation flow reactor concept, which involves a tight packing of stacked Nanosprings disks. For the investigated membranes, the density of immobilized enzymes was close to the reported value of capacity. From these experimental results, calculations on (maximally achievable) productivity of microreactors were made. This was combined with results of glucose oxidase immobilization on Nanosprings. The objective was to achieve high enzyme loadings to obtain reasonable space–time yields to ensure cost-effectiveness of the derived chemical reaction processes. These productivities were benchmarked to industrial production needs for two processes – a high-value pharmaceutical intermediate synthesis (towards chiral amino alcohols, using threonine aldolase) and a large-volume fine-chemical synthesis (the gluconic acid synthesis, using glucose oxidase), including suggestions for reactor scale-up. This shows that the present loading performance suffices in the case of high-value products, such as pharmaceuticals, but not for larger-volume, low-cost chemicals; at least under best-performance assumptions such as the avoidance of mass-transfer limitations.

Flow processes with microstructured reactors allow paradigm changes in process development and thus can enable a faster development time to the final production plant. They do this by exploiting similarity effects along the development chain (modularity) and intensification. The final result can be a (significantly) reduced number of apparatus in the plant, a (significantly) reduced apparatus size, and a higher predictability in the scale-out of the apparatus. So far, this was mainly achieved via transport intensification given in microstructured reactors – improved mixing and heat transfer which increase productivity and possibly improve selectivity. A more new idea is chemical intensification through deliberate use of harsh chemistries at unusual (high) pressure, temperature, concentration, and reaction environment which again increases productivity. A very new idea is the process design intensification – the reaction-maximized flow processes need less separation expenditure and the small unit size together with the high degree in functionality gives large potential for system integration. Both means change and simplify the process scheme totally which can lead to a reduced number of apparatus and has impact on predictability. The modular nature of the small flow units allow an easy implementation to modern modular plant environments (Future Factories) which enables to perform all the testing cycles (lab, pilot, production) in one plant environment; an example are here container plants. All these measures have large potential for (much) decreased overall development time.

The eluent droplet size defines the number of sampling compartments in a continuously operated annular electrochromatograph and therefore influences separation efficiency. In this work, an assembly of two capillaries, a feeding capillary on the top and a receiving capillary placed under it, has been investigated to control droplet size. The receiving capillary prevents the liquid droplet formation beyond a critical size, which reduces the volume of sampling compartment as compared with the case of the electrolyte flow driven solely by gravity. With a receiving capillary, the electrolyte droplet size was reduced from 1.5 to 0.46¿mm. Further decrease of droplet size was not possible due to a so-called droplet jump upwards effect which has been observed on a hydrophilic glass surface with water. A typical electrolyte used in CAEC has high methanol content. In an attempt to improve the methanol-repellent properties of the glass surface, two approaches have been implemented: (i) self-assembled chemisorbed monolayers of an alkylsiloxane and (ii) fabrication of a nano-pin film. The methanol-repellent surface of the feeding capillary suppressed the droplet jump upwards effect. The surface remained methanol repellent in different solutions with lower polarity than that of water.