A Comprehensive Review on Current Microwave Chemistry

Green (sustainable) chemistry provides a framework for chemists, pharmacists, medicinal chemists and chemical engineers to design processes, protocols and synthetic methodologies to make their contribution to the broad spectrum of global sustainability. Green synthetic conditions, especially catalysis, are the pillar of green chemistry. Green chemistry principles help synthetic chemists overcome the problems of conventional synthesis, such as slow reaction rates, unhealthy solvents and catalysts and the long duration of reaction completion time, and envision solutions by developing environmentally benign catalysts, green solvents, use of microwave and ultrasonic radiations, solvent-free, grinding and chemo-mechanical approaches. 1,2,4-thiadiazole is a privileged structural motif that belongs to the class of nitrogen–sulfur-containing heterocycles with diverse medicinal and pharmaceutical applications. This comprehensive review systemizes types of green solvents, green catalysts, ideal green organic synthesis characteristics and the green synthetic approaches, such as microwave irradiation, ultrasound, ionic liquids, solvent-free, metal-free conditions, green solvents and heterogeneous catalysis to construct different 1,2,4-thiadiazoles scaffolds.

Many experimental results regarding Arrhenius plot on various chemical reactions under microwave irradiation have been reported. According to these results, it can be confirmed in a wide variety of researching fields on chemistry that gradient and/or intercept of Arrhenius plot are changed depending on presence or absence of microwave irradiation. From this phenomenological universality on changes in gradient and/or intercept and invariance of linearity of Arrhenius plot under microwave irradiation, it can be expected that these changes in Arrhenius plot are appropriate as quantitative definition of chemical reaction accelerating effects under microwave irradiation. In experiment in this study, in order to quantitatively evaluate chemical reaction accelerating effects as microwave-specific non-thermal effect, base hydrolysis reactions of ester, benzyl isobutyrate, as a common organic chemical reaction were performed under isothermal condition for each reaction temperature (40, 50, 60°C) in both presence and absence of TE10-mode continuous microwave irradiation condition (2.45 GHz, 50 W). By controlling reaction system temperatures by thermal transmission with microwave non-absorbing refrigerant, kerosene, while flowing in outer tube of double tube glass test tube, the reaction temperatures were kept at each target reaction temperature throughout the reactions with sufficiently high precision whether presence or absence of microwave irradiation. By using fiber optic thermometer for monitoring bulk temperatures of each reaction system and by pre-heating each reaction system before adding reaction substrate to initiate reaction, the discussions about microwave thermal effects in reaction progressing stage and reaction system temperature rising stage were excluded accurately. The quantitative evaluation of chemical reaction accelerating effects as microwave-specific non-thermal effect on the performed hydrolysis reaction was conducted by using extended Arrhenius equation proposed based on the phenomenological changes in Arrhenius plot commonly confirmed in various types of reactions. As the result of this experiment, two types of correction coefficient of formula of Arrhenius plot for applying microwave irradiating reaction condition, “enthalpic effect coefficient” CH and “entropic effect coefficient” CS, were obtained as the chemical reaction accelerating effects from the analysis on gradient and intercept of experimentally drawn Arrhenius plot. The linearities of Arrhenius plots were sufficiently appropriate with or without microwave irradiation. In addition to confirming the chemical reaction accelerating effects under microwave irradiation on the performed hydrolysis reaction, from comparing between the orders of experimentally obtained values of CH and CS, it was suggested as one of the mechanisms of microwave-assisted chemistry that microwaves affect not on activation enthalpy ΔH°‡ and activation entropy ΔS°‡ separately, but on both values in the same mechanism caused by affecting on activation Gibbs free energy ΔG°‡ with microwaves. According to this suggestion, another definition of chemical reaction accelerating effect under microwave irradiation, “work effect coefficient” CG, was also proposed based on transition state theory in addition to CH and CS. From the results in this study as demonstration of leveraging extended Arrhenius equation, it is expected that the methodology in this study using extended Arrhenius equation including CH and CS is able to contribute to develop knowledge in the fields on microwave-assisted chemistry.

Abstract: The diverse field of chemistry demands various greener pathways in our quest to maintain sustainability. The utilization of energy inputs (mechanochemistry, ultrasound, or microwave irradiation), photochemistry, and greener reaction media being applied to organic synthesis are the key trends in the greener and sustainable process development in the current synthetic chemistry. These strategic methods aim to address the majority of the green chemistry principles, developing functional chemicals with less amount of waste production. In the synthesis of biologically potential heterocyclic molecules, green chemistry is a topic of great interest. It encompasses all branches of chemistry and is found in the notion of conducting chemical reactions while also conserving the environment through pollution-free chemical synthesis. Water as a solvent media is an excellent choice of solvent in organic synthesis development in the present day, as it is highly abundant, nontoxic, and non-combustible. Medicinal chemists have recently focused their attention on environmentally friendly procedures that use greener solvent media. Using water as a solvent, several studies on the process of optimization and selectivity have been reported, and the combination with microwave irradiation has emerged as a green chemistry protocol to produce high atom economy and yields. In this review, we have compiled microwave-assisted organic synthesis in aqueous media, including examples of the most cutting-edge methodologies employed for the heterocyclic scaffolds used in medicinal chemistry. It covers the most valuable advanced synthetics taking place in the area of heterocyclic molecule synthesis, between the decennary period of 2012 to 2021. The reported work discusses both synthetic and pharmacological applications.

Effect of microwave irradiation on the breaking and linear cutting of hard rock

Microwaves in Organic Synthesis

The use of microwave (MW) irradiation to increase the rate of chemical reactions has attracted much attention recently. However, the intrinsic nature of the effects of MW irradiation on chemical reactions remains unclear. Herein, the highly efficient conversion of NO and decomposition of H2S via MW catalysis were addressed. The reaction temperature was decreased by several hundred degrees centigrade. Moreover, the apparent activation energy (Ea′) decreased substantially under MW irradiation. Importantly, a model explaining the interactions between microwave electromagnetic waves and molecules is proposed to elucidate the intrinsic reason for the reduction in the Ea′ under MW irradiation, and a formula for the quantitative estimation of the decrease in the Ea′ was determined. MW irradiation energy was partially transformed to reduce the Ea′, highlighting that MW irradiation is a new type of power energy for speeding up chemical reactions. The effect of MW irradiation on chemical reactions was determined. Our findings challenge both the classical view of MW irradiation as only a heating method and the controversial MW non-thermal effect and open a promising avenue for the development of novel MW catalytic reaction technology. We have developed microwave catalysis for application in energy and environmental catalytic reactions. We have also developed microwave catalytic oxidation reaction technology for the degradation of organics in wastewater.

Multi-component reactions for the construction of heterocycles have been fascinated by microwave energy as an alternative technique of heating, owing to the advantages over traditional reflux methods. The heterogeneous catalysts contribute significantly towards recycling, harmless, easy filtration, catalyst preparation, more life span, abundance, and product yields. With novel and creative uses in organic and peptide synthesis, polymer chemistry, material sciences, nanotechnology, and biological processes, the usage of microwave energy has rapidly increased during the past 20 years. This article covers multicomponent reactions involving construction of chromenes, pyridines, pyrroles, triazoles, pyrazoles, tetrazoles, trans and cis julolidines using heterogeneous catalysts under microwave. It provides an overview of contemporary microwave-assisted heterogeneous catalytic reactions. Microwave chemistry is now an established technology with several advantages regarding reaction rate and production yield, improving energy savings as confirmed by many applications. Due to the widespread curiosity in medicinal chemistry, the heterogeneously catalysed construction of heterocycles under microwave irradiation is explored to reduce time and energy. By considering various aspects of economy, eco-friendly, and user-friendly factors, this review focuses on recent advances in the multi-component construction of heterocycles using heterogeneous catalysts under microwave irradiation. This review also discusses the benefits and limitations of reaction conditions and yields from the literature reports for the past five years.

Considering the very important medicinal and biological properties of heterocycles including isatin skeleton, synthesis of isatin-containing compounds has attracted the attention of medicinal and organic chemists, especially researchers involved in the synthesis of heterocycles. The present review focuses on the recent investigation in the synthesis of heterocycles with isatin moiety using isatin derivatives as reaction reactants via multi-component for the period of 2014–2024. The reports were classified according to the conditions of the reactions, which distinguishes this review from similar studies. In some reports, green chemistry has been used, such as the use of green solvent, green and reusable catalyst, solvent-free conditions, microwave irradiations and ultrasonic irradiations. Most reviews of isatin published so far have focused only on spirooxindoles, but this review not only addresses the condition for the synthesis of spirooxindoles, but also the synthesis of other isatin-contaning heterocycles such as pyrroloquinolines, imidazole-indoles and pyrazoloquinoline. The main objective of this review is to present an overview of the latest methodologies involving isatin in the multicomponent synthesis of heterocyclic compounds, specifically for organic and medicinal chemists.

Amide linkages are present in key natural products and in many biologically active molecules. Therefore, the formation of amide bonds is important to both synthetic chemists and biologists. Approximately 66% of all preliminary screening reactions in industrial medicinal chemistry laboratories involve amide formation. Although many methods have been developed for amide synthesis, a procedure for the direct coupling of amines with an acid in the presence of coupling agents without prior activation would be useful for building small-molecule libraries and for key steps in total syntheses. Condensing agents such as carbodiimides or other activating agents are generally employed under dry conditions. However, the condensing agent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4methylmorpholium chloride (DMT-MM) can be used to prepare carboxamides in alcohol or water. This reaction is technically simple and relatively easy to implement, requiring only a mixing of acids, amines, and DMTMM in MeOH or H2O. The synthesis of DMT-MM is also relatively simple, and it can be prepared from CDMT (2chloro-4,6 dimethoxy-1,3,5-triazine) and N-metheylmorphorine (NMM) in THF. The current report describes the application of microwave-induced acceleration to further improve the reaction conditions for amide synthesis using DMT-MM. Highspeed synthesis using microwave technology has attracted considerable attention in organic chemistry. Microwave irradiation provides advantages over conventional heating for chemical transformations, including accelerated reaction rates (and consequently reduced reaction times), higher yields, and cleaner reactions. These advantages led us to evaluate the use of microwave irradiation for amidation reactions involving less reactive secondary and primary amines with acid in the presence of DMT-MM. We also compared the effectiveness of dicyclohexylcarbodiimide (DCC), a well-known condensing reagent, when coupled with microwave irradiation versus classical thermal methods. The reactions were performed by dissolving amines, carboxylic acids, and the condensing agent in solvent, followed by irradiation in a temperature-controlled microwave oven. For comparison, the same reactions were carried out under conventional heating conditions. The amidation of 2-phenylethylamine (a primary amine) with substituted benzoic acid in the presence of DMT-MM in MeOH gave a yield of over 90% products within 25 min at 110 C with microwave irradiation. The reaction time with conventional heating was seven times that with microwave irradiation, and the yield was less than 10-20% of the yield with the microwave-assisted method. The reaction of piperidine (a secondary amine) with benzoic acid afforded a 91% yield within 30 min at 150 C with microwave irradiation; note the higher reaction temperature and longer reaction time compared with those of the primary amine reaction. Amidation of piperidine with substituted benzoic acid in the presence of DCC with pyridine in THF yielded more than 60% products within 25 min at 120 C with microwave irradiation. Thus, DMT-MM was a much more effective coupling agent than DCC. Further increases in reaction temperature were limited by the potential of solvents for producing an explosive atmosphere within the micro-

2-pyridones are important heterocycles with great applicability in medicinal chemistry and this core structure can be found in compounds with various biological/medicinal applications. Here we show how microwave-assisted chemistry can be used to effectively synthesize and functionalize substituted monocyclic 2-pyridones, 2-quinolones and other ring-fused 2-pyridones. The chapter covers recent advancements in this field mainly describing methods developed with instruments specially designed for microwave-assisted organic synthesis (MAOS).

In the Conventional laboratory or industry heating technique involve Bunsen burner, heating mental/hot plates and electric heating ovens. To produce a variety of useful compounds for betterment of mankind, the Microwave Chemistry was introduced in year 1955 and finds a place in one of the Green chemistry method. In Microwave chemistry is the science of applying microwave radiation to chemical reactions. Microwaves act as high frequency electric fields and will generally heat any material containing mobile electric charges, such as polar molecules in a solvent or conducting ions in a solid. Polar solvents are heated as their component molecules are forced to rotate with the field and lose energy in collisions i.e. the dipole moments of molecules are important in order to proceed with the chemical reactions in this method. It can be termed as microwave-assisted organic synthesis (MAOS), Microwave-Enhanced Chemistry (MEC) or Microwave-organic Reaction Enhancement synthesis (MORE). Microwave-Assisted Syntheses is a promising area of modern Green Chemistry could be adopted to save the earth.

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.

Microwave-assisted chemical reactions have attracted significant attention over many years, primarily because the microwave heating mechanism, so-called dielectric heating, is quite different from conventional conduction heating. Microwave heating has two interesting features: internal heating and selective heating. The internal heating takes place because microwaves propagate deeply into materials and simultaneously generate heat on both their internal and external regions. Selective heating is caused by dielectric property of materials. Microwaves can heat the material more preferably with a larger dielectric loss. These features will lead to shorter chemical reaction time and more efficient reaction.Since a microwave oven was invented nearly 70 years ago, a vacuum tube device i.e. magnetron has accounted for an overwhelming share of microwave heating applications. High-power semiconductors, on the other hand, are rapidly developing throughout the 21st century. Semiconductor-type microwave ovens with LDMOS have been developed these days. Although they are still inferior to the magnetron in cost and output power, the high-power semiconductors are expected to enhance microwave heating applications, especially microwave-assisted chemistry, thanks to their high spectrum purity, high frequency stability, wide frequency variability, and functionality.Semiconductor amplifiers will work more effectively in a resonant-type (so-called single mode) applicator than magnetrons because of their aforementioned features. In a single mode applicator with a high-quality resonator, microwaves can heat materials the most efficiently at the resonant frequency. Then frequency stability and adjusting capability are quite important because the resonator has narrow passband and the resonant frequency is easily shifted due to physical properties and volume of the materials. Hence semiconductor amplifiers are more suitable than magnetrons as a microwave power source of the single mode applicator.With respect to frequency allocation, the ISM bands of 2.45 GHz or 915 MHz (only used in several countries) are generally used for microwave heating. However these frequency bands are not always optimal for chemical processing because permittivity and permeability of materials are dependent on frequency and temperature as well as their physical and chemical properties. For this reason, we have developed batch-type microwave heating applicators which one can irradiate liquid samples with microwaves over a wide frequency range from 800 MHz to 2.7 GHz. Then high-power semiconductor amplifiers play an essential role in examining chemical reactions by using our developed applicators, which the magnetron can never assume.A challenging problem on microwave-assisted chemistry is scale-up of the microwave applicators for high-volume production. High-power, highly-efficient and compact semiconductor amplifiers, especially with AlGaN/GaN power devices, will contribute greatly to commercialization of microwave-assisted chemistry.In the present paper, we introduce availability of the high-power semiconductors in the microwave-assisted chemistry field.

4,4′-substituted-2,2′-((hexahydro-1H-benzo[d]imidazole-1,3(2H)-diyl)bis(methylene))bisphenols (1a–d) and 2,6-bis{[3-(2-hydroxy-5-substitutedbenzyl)octahydro-1H-benzimidazol-1-yl]methyl}-4-substitutedphenols (2a–b) were synthesized via microwave (MW) irradiation of aminal (2R,7R,11S,16S)-1,8,10,17-tetraazapentacyclo[8.8.1.1.8,170.2,70.11,16]icosane 2 with p-substituted phenols. Microwave (MW) irradiation improved reaction rates and yields at 80 °C. Compounds 1a–d were racemic, and 2a–b were diastereomeric. NMR spectra revealed key signals for the perhydrobenzimidazole fragment, aromatic rings, and aminal carbons. Differences in the 13C NMR spectra highlighted structural variations, such as distinct carbonyl and methoxyl signals in 2d. MW irradiation at higher temperatures (100–120 °C) reduced yields of 1, especially for phenols with methyl (Me) and methoxy (OMe) groups, suggesting a shift toward the formation of compound 2. Additionally, higher temperatures led to polymerization byproducts, emphasizing the impact of MW energy on reaction pathways. These results provide valuable insights for designing molecules with potential applications in materials science and medicinal chemistry.

This study explores the influence of microwave (MW) irradiation time on the NO<sub>2</sub> gas sensing performance of ZnO nanoparticles (NPs). ZnO NPs were subjected to MW irradiation for 1, 3, 5, and 7 minutes to assess the effects of defect engineering via MW irradiation on their sensing behavior. Phase and morphological characterizations using XRD and SEM confirmed that MW irradiation did not induce significant changes in the crystalline phase or surface morphology of the ZnO NPs. However, PL, XPS, TEM, and EDS results revealed the generation of defects, which were particularly pronounced after five minutes of MW exposure. The pristine ZnO NPs sensor displayed a response of 6.0 to 2 ppm NO<sub>2</sub> at 250 °C. After five minutes of MW irradiation, the response nearly doubled to 11.25 under the same conditions and reached 34.63 at 10 ppm NO<sub>2</sub>. The improved sensitivity was attributed to the formation of defect sites, ZnO-ZnO homojunctions, and ZnO-Zn(OH)<sub>2</sub> heterojunctions. Notably, the sensor irradiated for five minutes also demonstrated excellent selectivity toward NO<sub>2</sub> in the presence of interfering gases. These results demonstrate that MW-assisted defect modulation is a promising and scalable strategy to boost sensing features of ZnO NPs. It is anticipated that high-efficiency sensors tailored for specific environmental and industrial applications could be developed with further optimization of MW parameters and integration with surface modification techniques.