Microwave Flow: A Perspective on Reactor and Microwave Configurations and the Emergence of Tunable Single‐Mode Heating Toward Large‐Scale Applications

Microwave heating in chemical reactions was first reported in 1986. There have since been many reports employing microwave heating in organic chemistry, where microwave heating has afforded higher yields of products in shorter time periods. However, such reactions are challenging to scale in batch due to the limited penetration depth of microwaves as well as the wave propagation dependence on cavity size. Continuous flow has addressed both these issues, enabling scalability of microwave processes. As such, a host of reports employing microwave flow chemistry have emerged, employing various microwave heating and reactor configurations in the context of either custom‐built or commercial apparatus. The focus of this review is to present the benefits of microwave heating in the context of continuous flow and to characterize the different types of microwave flow apparatus by their design (oscillator, cavity type and reactor vessel). We advocate the adoption of tunable, solid‐state oscillator single‐mode microwave flow reactors which are more versatile heaters, impart better process control and energy efficiency toward laboratory and larger‐scale synthetic chemistry applications.     

Microwave-assisted enzyme-catalyzed reactions in various solvent systems

The work describes the accelerated enzymatic digestion of several proteins in various solvent systems under microwave irradiation. The tryptic fragments of the proteins were analyzed by matrix-assisted laser desorption/ionization mass spectrometry. Under the influence of rapid microwave heating, these enzymatic reactions can proceed in a solvent such as chloroform, which, under traditional digestion conditions, renders the enzyme inactive. The digestion efficiencies and sequence coverages were increased when the trypsin digestions occurred in acetonitrile-, methanol- and chloroform-containing solutions that were heated under microwave irradiation for 10 min using a commercial microwave applicator. The percentage of the protein digested under microwave irradiation increased with the relative acetonitrile content, but decreased as the methanol content was increased. These observations suggest that acetonitrile does not deactivate the enzyme during the irradiation period; in contrast, methanol does deactivate it. In all cases, the digestion efficiencies under microwave irradiation exceed those under conventional conditions.     

Microwave synthesis of nanoporous materials.

Studies in the last decade suggest that microwave energy may have a unique ability to influence chemical processes. These include chemical and materials syntheses as well as separations. Specifically, recent studies have documented a significantly reduced time for fabricating zeolites, mixed oxide and mesoporous molecular sieves by employing microwave energy. In many cases, microwave syntheses have proven to synthesize new nanoporous structures. By reducing the times by over an order of magnitude, continuous production would be possible to replace batch synthesis. This lowering of the cost would make more nanoporous materials readily available for many chemical, environmental, and biological applications. Further, microwave syntheses have often proven to create more uniform (defect-free) products than from conventional hydrothermal synthesis. However, the mechanism and engineering for the enhanced rates of syntheses are unknown. We review the many studies that have demonstrated the enhanced syntheses of nanoporous oxides and analyze the proposals to explain differences in microwave reactions. Finally, the microwave reactor engineering is discussed, as it explains the discrepancies between many microwave studies.     

Microwave-induced organic reaction enhancement (more) chemistry: Techniques for rapid,safe and inexpensive synthesis

Synthetic organic reactions have been conducted under microwave irradiation in open vessels in unaltered domestic microwave ovens. Reaction times vary from a few seconds for sub-milligram reactions to about 15 minutes for reactions carried out on a scale of hundreds of grams. Promising results have been obtained for several condensations, as well as the Bischler-Napieralski reaction, the Wolff-Kishner reduction, free radical dehalogenation reactions, and other standard synthetic operations. Rapid catalytic transfer hydrogenation using ammonium formate as the source of hydrogen has been conducted at about 100-130 °C under microwave irradiation. Meaningful, safe and inexpensive synthetic experiments for undergraduate and pre-college students have been developed and tested. The MORE chemistry techniques make it possible to use simple apparatus and very short reaction times. Commercial microwave ovens are now essential equipment in our research and teaching laboratories [1-3]. These ovens are relatively inexpensive, easy to move from one laboratory and set up in another, and safe to operate. Glass, plastics, and ceramics are essentially transparent to microwaves whereas many organic compounds are dipolar in nature and absorb microwave energy readily. We have found that untraditional experimental arrangements are possible for conducting a wide variety of organic reactions in open vessels inside domestic microwave ovens. Depending on the quantity of reactants, most reactions (on a scale of milligrams to several grams) can be completed in minutes instead of hours. One important element of our “Microwave-induced Organic Reaction Enhancement” (MORE) chemistry is the proper choice of a microwave energy transfer agent as the reaction medium.     

Practical and Scalable Organic Reactions with Flow Microwave Apparatus

Microwave irradiation has been used for accelerating organic reactions as a heating method and has been proven to be useful in laboratory scale organic synthesis. The major drawback of microwave chemistry is the difficulty in scaling up, mainly because of the low penetration depth of microwaves. The combination of microwave chemistry and flow chemistry is considered to overcome the problem in scaling up of microwave‐assisted organic reactions, and some flow microwave systems have been developed in both academic and industrial communities. In this context, we have demonstrated the scale‐up of fundamental organic reactions using a novel flow microwave system developed by the academic‐industrial alliance between the University of Shizuoka, Advanced Industrial Science and Technology, and SAIDA FDS. In this Personal Account, we summarize the recent progress of our scalable microwave‐assisted continuous synthesis using the SAIDA flow microwave apparatus.     

Application of advanced nuclear analytical techniques for the electrocatalyst's characterization: Paving the path for mechanistic investigations

As the application of electrocatalyst continues to expand, envisaging the hidden mechanisms occurring at various length scale affecting the catalytic efficiency became important. To enhance the stability of electrocatalyst and reduce the cost, it is of paramount importance to reveal the active site's dynamics (using in situ techniques for getting the real-time information) which directly affect the reactions such as oxygen evolution reaction, hydrogen evolution reaction, and so on. Since such reactions are crucial for many engineering and scientific applications, in situ characterization techniques are required, which could capture such reactions happening at a different length and time scale. This article analyzes the recent progress made in the field of electrocatalyst's characterization using in situ neutron techniques. The article also paves the future path and has delineated the future challenges involved in multiscale correlative techniques (e.g., neutron techniques in the combination of synchrotron or microscopic techniques) used for getting the multiscale (atomic to micrometer range) mechanistic information about the electrocatalyst's working and degradation.     

Prototyping an ionization source for non-engineers

Novel mass spectrometry (MS) based analytical platforms have enabled scientists to detect and quantify molecules within biological and environmental samples more accurately. Novel MS instrumentation starts as a prototype and, after years of development, can become a commercial product to be used by the larger MS community. Without the initial prototype, many MS-based instruments today would not be produced. Additionally, biotechnology companies are the main drivers for research, development, and production of novel instruments, but the tools for prototyping instrumentation have never been more accessible. Here, we present a tutorial on prototyping instrumentation through the case study of developing the Next Generation IR-MALDESI source to show that an engineering degree is not required to design and construct a prototype instrument with modern hardware and software. We discuss the prototyping process, the necessary skills required for efficient prototyping, and information about common hardware and software used within initial prototypes.     

微波辐射-酶耦合催化(MIECC)反应

将微波辐射用于非水相酶催化可以获得很多有别于常规加热下的反应结果。本文讨论了微波的非热效应在酶促反应中的表现,探讨了微波辐射对酶的结构、构象、活性及酶催化反应动力学的影响,以及微波辐射-酶耦合催化对反应的对映选择性、底物专一性、前手性选择性和区域选择性的影响。在大多数场合,适当的微波辐射不会损伤酶活而且可以提高反应速率,而对酶特异性的影响则不一而论。     

Microwave synthesis of zeolites. 2. Effect of vessel size, precursor volume, and irradiation method

The enhancement of synthesis reactions under microwave heating is dependent on many complex factors. We investigated the importance of several reaction engineering parameters relevant to microwave synthesis. Of interest to this investigation were the reaction vessel size, volume of precursor reacted, microwave power delivery, and microwave cavity design. The syntheses of NaY zeolite and beta-zeolite were carried out under a number of varying conditions to determine the influence of these parameters on the nucleation rate, the crystallization rate, and the particle size and morphology. The rates of NaY and beta-zeolite nucleation and crystallization were more rapid in the multimode CEM MARS-5 oven compared to the more uniform field CEM Discover. The faster synthesis rate in the MARS-5 may be the result of the multimode microwave electric field distribution. Slower rates of NaY and beta-zeolite formation observed in the Discover and a circular waveguide may be the result of a more uniform microwave electric field distribution. Changes in reaction vessel size and precursor volume during the microwave synthesis of beta- and NaY zeolite were found to influence the rate of zeolite formation. These results indicate that reactor geometry needs to be considered in the design of systems used for microwave synthesis. Comparative synthesis reactions were carried out with conventional heating, and microwave heating was shown to be up to over an order of magnitude faster for most of these syntheses.     

Inductive heating with magnetic materials inside flow reactors

Superparamagnetic nanoparticles coated with silica gel or alternatively steel beads are new fixed-bed materials for flow reactors that efficiently heat reaction mixtures in an inductive field under flow conditions. The scope and limitations of these novel heating materials are investigated in comparison with conventional and microwave heating. The results suggest that inductive heating can be compared to microwave heating with respect to rate acceleration. It is also demonstrated that a very large diversity of different reactions can be performed under flow conditions by using inductively heated flow reactors. These include transfer hydrogenations, heterocyclic condensations, pericyclic reactions, organometallic reactions, multicomponent reactions, reductive cyclizations, homogeneous and heterogeneous transition-metal catalysis. Silica-coated iron oxide nanoparticles are stable under many chemical conditions and the silica shell could be utilized for further functionalization with Pd nanoparticles, rendering catalytically active heatable iron oxide particles.     

Small molecule library synthesis using segmented flow

Flow chemistry has gained considerable recognition as a simple, efficient, and safe technology for the synthesis of many types of organic and inorganic molecules ranging in scope from large complex natural products to silicon nanoparticles. In this paper we describe a method that adapts flow chemistry to the synthesis of libraries of compounds using a fluorous immiscible solvent as a spacer between reactions. The methodology was validated in the synthesis of two small heterocycle containing libraries. The reactions were performed on a 0.2 mmol scale, enabling tens of milligrams of material to be generated in a single 200 mL reaction plug. The methodology allowed library synthesis in half the time of conventional microwave synthesis while maintaining similar yields. The ability to perform multiple, potentially unrelated reactions in a single run is ideal for making small quantities of many different compounds quickly and efficiently.     

微波固相法合成层状磷锑酸钾化合物

应用微波合成技术, 以石墨或三氧化二铁为加热介质, 合成了两种新的层状磷锑酸钾: KSbP2O8, K3Sb3P2O14。与传统固相反应相比较(典型合成条件为:950~1000℃下、24h), 微波法可在微波辐射下(2.45 GHz), 仅在40~90分钟内使反应完成。在详细研究相转变的同时, 对微波在固相合成中的作用进行了初步的讨论。     

Microwave Synthesis of SAPO‐11 and AlPO‐11: Aspects of Reactor Engineering

AlPO‐11 and SAPO‐11 are synthesized using microwave heating. The effects of precursor volume, reaction temperature, reactor geometry, stirring, applicator type and frequency on the microwave synthesis of SAPO‐11 and AlPO‐11 are studied. The nucleation time and crystallization rate are determined from crystallization curves for SAPO‐11 (and/or AlPO‐11), for the various parameters investigated. Increasing volume of the reacting material decreases the reaction rate of SAPO‐11 at 160°C. In particular, the nucleation time increases with increase in the reaction volume. Increasing the reaction temperature increases the crystallization rate and decreases the nucleation time, however it decreases the particle size. Nucleation of SAPO‐11 and AlPO‐11 under microwave heating is strongly dependant on the reaction temperature. Using wider geometry vessel (33 mm compared to 11 mm diameter) enhances the reaction rate, producing larger crystals in the same reaction time, even though the crystallization rate is decreased. The crystallization rate is enhanced by applicator type in the following order CEM MARS‐5 oven>CEM Discover “focused” system>monomode waveguide. Stirring the reacting solution during heating affects primarily the nucleation time. The effect of microwave frequency on the nucleation and growth of SAPO‐11 shows a dependence on the applicator type more than the specific frequency, for the frequency range 2.45–10.5 GHz. The difference between the crystallization rate observed at higher frequencies and that at 2.45 GHz maybe due to the multimode nature of the waveguide at frequencies above 2.45 GHz. Sweeping the microwave frequency linearly between 8.7 and 10.5 GHz at rates of 10 min^?1 and 100 min^?1 shows an intermediate crystallization curve to that for fixed frequencies of 2.45 GHz and that for 5.8, 8.7 and 10.5 GHz.     

Microwave-assisted organic synthesis in microstructured reactors

The coupling of microwave heating with microprocessing in continuous-flow reactors has been reviewed in various organic synthesis reactions. The fast growing field of microwave and microreactor technology has a significant impact on the development of fine chemicals industry. Both technologies offer not only the possibility of realizing many of the individual advantages integrated into one combined system, but also the potential of eliminating the major hurdle of a limited microwave penetration depth for large-scale chemical synthesis. Metal film-coated capillary microreactors allow creation of local hot spots to achieve temperatures far in excess of the solvent temperature, which accelerates chemical reactions under MW heating.     

Influence of polarity on the scalability and reproducibility of solvent-free microwave-assisted reactions

Organic reactions performed in the absence of solvent in domestic ovens without appropriate temperature control are generally considered as not reproducible, particularly when different instruments are used. For this reason, reproducibility has historically been one of the major issues associated with Microwave-Assisted Organic Synthesis (MAOS) especially when domestic ovens are involved. The lack of reproducibility limits the general applicability and the scale up of these reactions. In this work several solvent-free reactions previously carried out in domestic ovens have been translated into a single-mode microwave reactor and then scaled up in a multimode oven. The results show that most of these reactions, although not considered as reproducible, can be easily updated and applied in microwave reactors using temperature-controlled conditions. Furthermore, computational calculations can assist to explain and/or predict whether a reaction will be reproducible or not.     

Membranes and theoretical modeling of membrane distillation: a review

Membrane distillation (MD) is one of the non-isothermal membrane separation processes used in various applications such desalination, environmental/waste cleanup, food, etc. It is known since 1963 and is still being developed at laboratory stage for different purposes and not fully implemented in industry. An abrupt increase in the number of papers on MD membrane engineering (i.e. design, fabrication and testing in MD) is seen since only 6 years ago. The present paper offers a comprehensive MD state-of-the-art review covering a wide range of commercial membranes, MD membrane engineering, their MD performance, transport mechanisms, experimental and theoretical modeling of different MD configurations as well as recent developments in MD. Improved MD membranes with specific morphology, micro- and nano-structures are highly demanded. Membranes with different pore sizes, porosities, thicknesses and materials as well as novel structures are required in order to carry out systematic MD studies for better understanding mass transport in different MD configurations, thereby improving the MD performance and looking for MD industrialization.     

Enhancement of Chemical Reactions by Microwave Irradiation

Microwaves are low electromagnetic energy which induce molecular perturbation by stimulation of ionic diffusion and by enhancement of dipole rotation without causing rearrangement of molecular structures. Microwave energy irradiated on the samples in various liquid media is lost or absorbed to the samples by the following two mechanisms: ionic conduction and dipole rotation. These two effects take place simultaneously to account for the phenomenon of rapid heating associated with many practical applications of microwave irradiation. In contrast to conventional heating, the salient feat ure of “dipole rotation” constitutes one efficient form of “molecular agitation” or “molecular stirring” which can be explored for many aspects in chemical reactions. We will discuss some of the useful application of “molecular agitation” by means of microwave irradiation such as: 1. rapid hydrolysis of proteins and peptides, 2. selective hydrolysis of aspartyl peptide bond, 3. the racemization of amino acids, 4. rapid hydrolysis of sugars, 5. continuous-flow process of microwave reactions, and 6. the enhancement of coupling reactions in peptide synthesis.     

Microwave-assisted solvent-free lipase catalyzed transesterification of β-ketoesters

Abstract

Lipase-catalyzed transesterification was used as an efficient tool for the interconversion of β-ketoesters. Catalytic activity of commercial lipase B from Candida antarctica (Novozym 435) was evaluated in systems involving non activated acyl donors, and enhanced using microwave irradiation. Interestingly, the combination of CAL B in microwave irradiation worked excellent in solvent-free conditions, thus assuring a highly competitive and environment-friendly process with high yields (up to 96%) in competitive times (< 2h). The combination of biocatalysis with solvent-free systems and microwave assistance is currently scarcely used, and may represent a powerful synergy for preparative reactions.     

Reproducibility and scalability of solvent-free microwave-assisted reactions: from domestic ovens to controllable parallel applications

The heating of different parallel arrays in domestic ovens offers the possibility to perform multiple reactions in one irradiation experiment, blending the advantages of microwave heating technology and parallel chemistry. However, they are usually performed without an appropriate temperature control; thus, reproducibility becomes a major issue limiting the application of such reactions. This is exemplified when working at a different scales or using different instruments. For the first time a typical solvent-free reaction described in a domestic oven has been reproduced in monomode reactor, scaled up in a controlled multimode oven and reproduced in parallel, 24 reactions were carried out in a well plate. Parallel reactions were performed in a Weflon multiwell plate to assure identical conditions for each individual reaction. As many reactions under microwave irradiation have been performed in solvent-free conditions, this result opens new possibilities in reproducibility, scalability and combinatorial chemistry and permits to take advantage of many synthetic procedures described in domestic ovens.