Evolution of microwave irradiation and its application in green chemistry and biosciences

Microwave-assisted organic reactions have been applied as an effective technique in organic synthesis. Microwave irradiation often leads to shorter reaction times, increased yields, easier workup, matches with green chemistry protocols, and can enhance the region and stereo selectivity of reactions. In fact, the high usefulness of microwave-assisted synthesis encouraged us to increase the efficiency of several organic transformations and synthesis. High-speed microwave-assisted chemistry has attracted a considerable amount of attention in recent years and has been applied successfully in various fields of synthetic organic chemistry, proteins, peptides, drug discovery, and green chemistry. The various roles of microwave-assisted organic chemistry in green and sustainable chemistry are discussed, beginning with the strategies, technologies, and methods that were employed routinely at the time of the first reports of microwave applications. Microwave processing has several advantages over conventional sintering/heating, such as the reduction in cycle time, energy efficiency, eco-friendliness, and providing finer microstructures, leading to improved mechanical properties. Herein, we also describe the evolution of the microwave and some early applications of microwave assistance in the biomolecular sciences and treatment of solid malignant tumors.     

Controlled microwave heating in modern organic synthesis

Although fire is now rarely used in synthetic chemistry, it was not until Robert Bunsen invented the burner in 1855 that the energy from this heat source could be applied to a reaction vessel in a focused manner. The Bunsen burner was later superseded by the isomantle, oil bath, or hot plate as a source for applying heat to a chemical reaction. In the past few years, heating and driving chemical reactions by microwave energy has been an increasingly popular theme in the scientific community. This nonclassical heating technique is slowly moving from a laboratory curiosity to an established technique that is heavily used in both academia and industry. The efficiency of "microwave flash heating" in dramatically reducing reaction times (from days and hours to minutes and seconds) is just one of the many advantages. This Review highlights recent applications of controlled microwave heating in modern organic synthesis, and discusses some of the underlying phenomena and issues involved.     

Rapid synthesis and fluorous-phase purification of α-perfluorohexyloligothiophenes

A high-throughput methodology that facilitates the synthesis, purification and characterisation of π-conjugated oligothiophenes has been developed. α-Perfluorohexyltetrathiophene was synthesised by sequential α-bromination and microwave promoted Stille cross-coupling reactions. Each synthetic transformation was followed by a fluorous solid-phase extraction (F-SPE) procedure to isolate the desired α-perfluorohexyloligothiophene. After a single F-SPE, each oligomer gave essentially one peak by GC-MS, which enabled stepwise growth of a tetrathiophene with no additional purification of the intermediate building blocks required. We anticipate that microwave accelerated synthesis in conjunction with fluorous-phase purification of π-conjugated systems will find generic application in the high-throughput parallel-synthesis of novel organic materials for semiconductor applications.     

New alkyl derivatives phosphine sulfonate (P-O) ligands. Catalytic activity in Pd-catalysed Suzuki-Miyaura reactions in water

Two novel bis(o-methoxyphenyl) phosphinoalkylsulfonate (P-O) ligands have been prepared through a new and sustainable synthetic route; they are air stable as well as water soluble and have been applied in Pd-catalysed Suzuki-Miyaura cross-coupling reactions in neat water in conjunction with microwave heating.     

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.     

The applications of microwaves in chemical syntheses

The application of microwave dielectric heating techniques for chemical syntheses has attracted considerable interest in recent years. A fundamental understanding of the mechanisms responsible for effective coupling of microwave radiation to liquid and solid chemicals and the establishment of techniques for containing the chemicals safely within a microwave cavity have contributed to the rapid progress in this area. A wide range organic and inorganic reactions have been accelerated using microwave techniques. The rapid syntheses of these compounds can be attributed primarily to superheating effects which result from the effective coupling of microwaves to the polar organic solvent in the containment vessel. Similar methods have been used for accelerating intercalation reactions resulting in the incorporation of organic molecules between the layers of an inorganic host material. In the solid state mixed metal oxides may be synthesized at an accelerated rate if one of the components has a high loss tangent. The ceramic high temperature superconducting materials have been synthesized in this manner and have utilized the high loss tangent of copper oxide. Metal chlorides, chalcogenides and oxides have also been synthesized directly from the elements using microwave dielectric heating effects resulting from the efficient coupling of microwaves to the particles of metal powder.     

Efficient synthesis of functionalized 6-arylsalicylates via microwave-promoted Suzuki cross-coupling reaction

Functionalized 6-arylsalicylate substructures occur in a variety of pharmacologically relevant natural products and bioactive compounds. They are also broadly used as important intermediates in organic synthesis. Traditional synthetic methods have suffered from some drawbacks, such as relatively harsh reaction conditions, narrow range of substrates, and poor yields. Utilizing microwave irradiation, the synthesis of functionalized 6-arylsalicylates via a Suzuki cross-coupling has been developed with a wide range of substrates. Almost all the reactions proceeded smoothly and afforded moderate to excellent yields of products, which indicated that electronic effects and steric modifications have little effect on this reaction.     

Microwave-assisted reactions in heterocyclic compounds with applications in medicinal and supramolecular chemistry

Microwave irradiation has been successfully applied in organic chemistry. Spectacular accelerations, higher yields under milder reaction conditions and higher product purities have all been reported. Indeed, a number of authors have described success in reactions that do not occur under conventional heating and modifications in selectivity (chemo-, regio- and stereoselectivity) have even been reported. Recent advances in microwave-assisted combinatorial chemistry include high-speed solid-phase and polymer-supported organic synthesis, rapid parallel synthesis of compound libraries, and library generation by automated sequential microwave irradiation. In addition, new instrumentation for high-throughput microwave-assisted synthesis continues to be developed at a steady pace. The impressive speed combined with the unmatched control over reaction parameters justifies the growing interest in this application of microwave heating. In this review we highlight our recent advances in this area, with a particular emphasis on cycloaddition reactions of heterocyclic compounds both with and without supports, applications in supramolecular chemistry and the reproducibility and scalability of organic reactions involving the use of microwave irradiation techniques.     

Application of Microwave Heating Technique to Esterification

Introduction Although the application of microwave technique has been reported as a new type of energy source chemically, it is only in recent years that this technique has been used as the energy source for organic synthesis. In 1986, R. Gedye, et al., published the report of the benzoate synthesis from the respective reactions between benzene carboxylic acid and methanol, propanol or butanol under microwave heating and the catalysis of H_2SO_4.     

Palladium-Catalyzed Organic Reactions Involving Hypervalent Iodine Reagents

The chemistry of polyvalent iodine compounds has piqued the interest of researchers due to their role as important and flexible reagents in synthetic organic chemistry, resulting in a broad variety of useful organic molecules. These chemicals have potential uses in various functionalization procedures due to their non-toxic and environmentally friendly properties. As they are also strong electrophiles and potent oxidizing agents, the use of hypervalent iodine reagents in palladium-catalyzed transformations has received a lot of attention in recent years. Extensive research has been conducted on the subject of C—H bond functionalization by Pd catalysis with hypervalent iodine reagents as oxidants. Furthermore, the iodine(III) reagent is now often used as an arylating agent in Pd-catalyzed C—H arylation or Heck-type cross-coupling processes. In this article, the recent advances in palladium-catalyzed oxidative cross-coupling reactions employing hypervalent iodine reagents are reviewed in detail.     

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.     

Carbohydrate-derived porous carbon materials: An ideal platform for green organic synthesis

Porous carbon materials have attracted much attention in the field of organic synthesis in recent years,due to their tunable properties, excellent catalytic activity and stability. Biomass-based carbohydrates emerge as an ideal precursor for the generation of these materials owing to their renewability, low cost,non-toxicity and high content of functional groups. Thus, carbon materials prepared from carbohydrates is of considerable importance for the sustainable development of organic chemistry....     

Pd-catalyzed cross-coupling reactions of alkyl halides

Cross-coupling reactions have become indispensable tools for creating carbon-carbon (or heteroatom) bonds in organic synthesis. Like in other important transition metal catalyzed reactions, such as metathesis, addition, and polymerization, unsaturated compounds are usually employed as substrates for cross-coupling reactions. However during the past decade, a great deal of effort has been devoted to the use of alkyl halides as saturated compounds in cross-coupling reactions, which has resulted in significant progress in this undeveloped area by introducing new effective ligands. Many useful catalytic systems are now available for synthetic transformations based on C(sp(3))-C(sp(3)), C(sp(3))-C(sp(2)) and C(sp(3))-C(sp) bond formation as complementary methods to conventional C(sp(2))-C(sp(2)), C(sp(2))-C(sp) and C(sp)-C(sp) coupling. This tutorial review summarizes recent advances in cross-coupling reactions of alkyl halides and pseudohalides catalyzed by a palladium complex.     

Highly functionalized organomagnesium reagents prepared through halogen-metal exchange

Organomagnesium reagents occupy a central position in synthetic organic and organometallic chemistry. Recently, the halogen-magnesium exchange has considerably extended the range of functionalized Grignard reagents available for synthetic purposes. Functional groups such as esters, nitriles, iodides, imines, or even nitro groups can be present in a wide range of aromatic and heterocyclic organomagnesium reagents. Also various highly functionalized alkenyl magnesium species can be prepared. These recent developments as well as new applications of organomagnesium reagents in cross-coupling reactions and amination reactions will be covered in this Review.     

Nonthermal microwave effects revisited: on the importance of internal temperature monitoring and agitation in microwave chemistry

The concept of nonthermal microwave effects has received considerable attention in recent years and is the subject of intense debate in the scientific community. Nonthermal microwave effects have been postulated to result from a direct stabilizing interaction of the electric field with specific (polar) molecules in the reaction medium that is not related to a macroscopic temperature effect. In order to probe the existence of nonthermal microwave effects, four synthetic transformations (Diels-Alder cycloaddition, alkylation of triphenylphosphine and 1,2,4-triazole, direct amide bond formation) were reevaluated under both microwave dielectric heating and conventional thermal heating. In all four cases, previous studies have claimed the existence of nonthermal microwave effects in these reactions. Experimentally, significant differences in conversion and/or product distribution comparing the conventionally and microwave-heated experiments performed at the same measured reaction temperature were found. The current reevaluation of these reactions was performed in a dedicated reactor setup that allowed accurate internal reaction temperature measurements using a multiple fiber-optic probe system. Using this technology, the importance of efficient stirring and internal temperature measurement in microwave-heated reactions was made evident. Inefficient agitation leads to temperature gradients within the reaction mixture due to field inhomogeneities in the microwave cavity. Using external infrared temperature sensors in some cases results in significant inaccuracies in the temperature measurement. Applying the fiber-optic probe temperature monitoring device, a critical reevaluation of all four reactions has provided no evidence for the existence of nonthermal microwave effects. Ensuring efficient agitation of the reaction mixture via magnetic stirring, no significant differences in terms of conversion and selectivity between experiments performed under microwave or oil bath conditions at the same internally measured reaction temperatures were experienced. The observed effects were purely thermal and not related to the microwave field.     

Fast, easy, clean chemistry by using water as a solvent and microwave heating: the Suzuki coupling as an illustration

Water is an excellent solvent for organic chemistry and microwave heating offers a very efficient way of heating reaction mixtures. In this article, by focusing on the Suzuki reaction, it is shown how these two methods, used alone or together, can impact modern synthetic chemistry, making reactions faster, easier and cleaner.     

微波与有机化学反应的选择性

本文综述了微波辅助下有机化学反应的选择性,包括化学选择性、区域选择性、顺反选择性、非对映选择性、对映选择性,与传统加热条件下反应选择性的区别。讨论了微波对有机化学反应选择性的影响。从文献报道的结果来看,虽然观察到了一些反应在微波照射与加热条件下显示出不同的选择性,但绝大部分例子并不是在严格相同的条件下进行的对比,还有一些虽然做了对比研究,但却忽略了温度的影响。对于绝大多数例子,微波产生的选择性的差别似乎都可以用热效应来解释。可以认为微波辅助的反应中基本不存在特殊的"非热效应"。微波辅助技术可以通过改变反应温度来实现改变某些反应的选择性。希望本文对微波效应和微波对有机反应加速效应的本质的理解提供一些有用信息。     

Microbial and Enzymatic Processes for the Production of Biologically and Chemically Useful Compounds [New Synthetic Methods (69)]

In recent years, the most significant development in the field of synthetic organic chemistry has been the application of biological systems to chemical reactions. Reactions catalyzed by enzymes and enzyme systems display far greater specificities than more conventional organic reactions. Biological and/or enzymatic syntheses and transformations, that is, “microbial transformations,” have great potential. Some of these reactions have already been shown to have useful applications in the fields of synthetic organic chemistry and biotechnology. This article reviews the current status of the rapidly developing field of microbial transformation, the methodology, available technological procedures, and fields of application being described especially in relation to conventional organic synthesis methods.     

Cross-metathesis assisted by microwave irradiation

Microwave irradiation effectively accelerates cross-coupling metathesis reactions between deactivated olefins. Reactions have been carried out with the phosphine-free Hoveyda-Grubbs catalyst and the "second generation Grubbs' catalyst." While there have been reports that a "microwave effect" is observed in various transformations, the accelerations we observe are due to the efficient and rapid heating and increased pressure in the microwave apparatus.     

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.