My Twenty Years in Microwave Chemistry: From Kitchen Ovens to Microwaves that aren't Microwaves

This Personal Account describes the author's involvement in the field of microwave‐assisted organic synthesis (MAOS) from the late 1990’s starting out with kitchen microwave ovens right through to the development of a reactor in 2016 that – although not using microwave technology – in many ways mimics the performance of a modern laboratory microwave. The reader is taken along a journey that has spanned two decades of intense research on various aspects of microwave chemistry, and, at the same time, was intimately linked to key innovations regarding equipment design and development. A “behind the scenes” approach is taken in this article to share – from a very personal point of view – how specific projects and research ideas were conceived and developed in my research group, and how in general the field of microwave chemistry has progressed in the last two decades.     

Microwave Intensified Synthesis: Batch and Flow Chemistry

Many studies have been conducted on organic and inorganic synthesis by microwave heating owing to its special heating mechanism, leading to improved reaction rate, higher purity and yields. We specifically demonstrated microwave heating in the fabrication of nanoparticles and polyester. By fine‐tuning the microwave and experimental parameters, the materials prepared have shown excellent physical and bio‐properties, e. g. narrow particle size distribution, controlled morphology, varied molecular structure and so forth. We further highlight the recent procedure of using fluidic reactors on preparing both metals and metal oxides nanoparticles. The experimental design strategies and fundamentals of the microwave interaction with chemicals are presented. Furthermore, the key factors and issues facing in this area are also discussed.     

流动化学在卤化反应中的应用

有机物的卤化反应是有机合成中最重要的转化之一.传统釜式卤化反应存在高放热及选择性差等问题,且卤化试剂一般具有毒性和腐蚀性.流动化学在传质和传热方面具有显著优势,可精确控制反应温度及试剂用量,并且可在线淬灭危险试剂,避免其暴露.按有机化合物卤化反应分类,系统地归纳了流动化学在氟化反应、氯化反应、溴化反应和碘化反应中的应用进展,并展望了其发展趋势.     

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.     

连续流动化学方法在无机制备科学中的应用

"连续流动化学"方法是无机制备科学中一种极具发展潜力的科学手段。作为一种已发展成熟的过程强化技术,与溶液合成、水热(溶剂热、离子热)等合成方法相比,"连续流动化学"方法具有可精确调控反应速度、缩短反应周期、优化并放大化学反应、提高产率的独特优势。本文总结了当前连续流动化学在无机物的分离和提取,纳米粒子、多金属氧酸盐等无机材料合成等领域的应用,分析了其在无机制备科学中存在的问题并展望了其的发展趋势。     

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.     

Rapid Optimization of Reaction Conditions Based on Comprehensive Reaction Analysis Using a Continuous Flow Microwave Reactor

Generally, the flow method has the advantage of a precise control over the reaction parameters and a facile modification of the reaction conditions, while a continuous flow microwave reactor allows for the quick optimization of reaction conditions owing to the rapid uniform heating. In this study, we developed a “9+4+1 method” to optimize reaction conditions based on comprehensive reaction analysis using a flow microwave reactor. The proposed method is expected to contribute to the synthesis of various fine and bulk chemicals by reducing cost and wastage, and by conserving time.     

Kinetic Determination of Ruthenium by on-line Microwave Flow Injection Analysis

ABSTRACT

A new rapid, high sensitive and selective on-line microwave flow injection method has been developed for the determination of micro-amounts of ruthenium, based on its catalytic effect on the oxidation of dibromocarboxyarsenazo (DBM-AsA) by potassium periodide in acidic medium. The assay is performed in a microwave-induced flow injection analyzer by measuring the absorption of DBM-AsA at 538 nm spectrophotometrically.     

Accelerating Spirocyclic Polyketide Synthesis using Flow Chemistry

Over the past decade, the integration of synthetic chemistry with flow processing has resulted in a powerful platform for molecular assembly that is making an impact throughout the chemical community. Herein, we demonstrate the extension of these tools to encompass complex natural product synthesis. We have developed a number of novel flow‐through processes for reactions commonly encountered in natural product synthesis programs to achieve the first total synthesis of spirodienal A and the preparation of spirangien A methyl ester. Highlights of the synthetic route include an iridium‐catalyzed hydrogenation, iterative Roush crotylations, gold‐catalyzed spiroketalization and a late‐stage cis‐selective reduction.     

High Refractive-Index Microspheres as Optical Cavity Structure

Microspheres of refractive index of n_D > 2.0 have been investigated. The organic-inorganic hybrid microspheres of n_D = 1.72 were prepared by the vibrating orifice technique using titanium-tetra-n-butoxide (TTBu) and diphenyldimethoxysilane (DPhDMS). For lasing demonstration, Eu³⁺-doped microspheres were prepared using europium (III) thenoyltrifluoroacetonate [Eu(TTFA)₃] as the dopant. The particles have good spherical shape, smooth surface and high optical transparency. The diameters of the particles could be controlled to within 0.1 m. Subsequent heating of the microspheres at 550°C under oxygen atmosphere resulted in an increase in the refractive index up to n_D = 2.6 with retention of the spherical shape. Resonant emission was confirmed from Eu^{3 +}-doped microspheres after heating at 400–550°C, by pumping with the 514.5 nm line of a CW- Ar⁺laser.     

Electromagnetic Relationship between Microwaves and Flow Reactor Systems

One of the important points in handling microwaves is that the order of magnitude is decimeter order. Laboratory equipment is not too big for wavelength, so intensity nonuniformity may occur. Another important point is that microwave propagation changes with material parameter changes. To heat material in the planned shape, the consideration with electromagnetism about the equipment and the system will be necessary. Herein, the phenomena which should be considered when a flow reactor is irradiated with a microwave is described.     

Fluoro-Substituted Methyllithium Chemistry: External Quenching Method Using Flow Microreactors

The external quenching method based on flow microreactors allows the generation and use of short-lived fluoro-substituted methyllithium reagents, such as fluoromethyllithium, fluoroiodomethyllithium, and fluoroiodostannylmethyllithium. Highly chemoselective reactions have been developed, opening new opportunities in the synthesis of fluorinated molecules using fluorinated organometallics.     

Flow Chemistry Meets Advanced Functional Materials

Flow chemistry and continuous processing techniques are beginning to have a profound impact on the production of functional materials ranging from quantum dots, nanoparticles and metal organic frameworks to polymers and dyes. These techniques provide robust procedures which not only enable accurate control of the product material’s properties but they are also ideally suited to conducting experiments on scale. The modular nature of flow and continuous processing equipment rapidly facilitates reaction optimisation and variation in function of the products.     

Estimation of Outlet Temperature of a Flow Reactor Heated by Microwave Irradiation

Flow reactors heated by microwave irradiation attract attention. The reactors are suitable for difficult synthesis processes due to rapid heating and cooling, and easy pressurization. In order to predict the quality of the product, it is appropriate to estimate the outlet conditions of the reactor. In this paper, the outlet temperature of the flow direction is estimated by using the flow condition and dynamic thermal energy balance of the reactor.     

Continuous‐Flow Microwave Synthesis of Metal–Organic Frameworks: A Highly Efficient Method for Large‐Scale Production

Metal–organic frameworks are having a tremendous impact on novel strategic applications, with prospective employment in industrially relevant processes. The development of such processes is strictly dependent on the ability to generate materials with high yield efficiency and production rate. We report a versatile and highly efficient method for synthesis of metal–organic frameworks in large quantities using continuous flow processing under microwave irradiation. Benchmark materials such as UiO‐66, MIL‐53(Al), and HKUST‐1 were obtained with remarkable mass, space–time yields, and often using stoichiometric amounts of reactants. In the case of UiO‐66 and MIL‐53(Al), we attained unprecedented space–time yields far greater than those reported previously. All of the syntheses were successfully extended to multi‐gram high quality products in a matter of minutes, proving the effectiveness of continuous flow microwave technology for the large scale production of metal–organic frameworks.     

A Review: Application of Microwave Techniques for Environmental Analytical Chemistry

Abstract

The acceptance of microwave digestion technique is based on procedures successfully carried out for mist different kinds of samples. The goals of this paper are to gather all information concerning applications of microwave digestion methods to analytical chemistry. Some applications of microwave techniques to sample digestion, solvent extraction, sample drying, the measurements of moisture, analyte desorption and adsorption, sample clean up, chromomeric reaction, speciation, and nebulization of analytical samples are presented.