Current Microwave Chemistry - Volume 10, Issue 2, 2023

Biginelli adducts, also known as dihydropyrimidin-2(1H)-ones/-thiones (DHMPs), exhibit versatile biological activities. Among them, monastrol has gained significant popularity as an inhibitor of kinesin-5 (Eg5), a motor protein crucial for spindle bipolarity. The inhibitory effect of monastrol on Eg5 accounts for its promising anticancer properties, along with its well-established role as an anti-inflammatory agent and calcium channel inhibitor. Since its first report in 1893, the Biginelli reaction has been extensively studied from various angles, including the scope of reagents used, the incorporation or omission of catalysts and solvents, and the application of innovative techniques like mechanochemical and ultrasonic reactors. Among these methods, microwave irradiation (MWI) has shown remarkable promise, aligning with the principles of green chemistry by offering solvent-free conditions, eco-friendly catalysts, and accelerated reaction times, ultimately leading to higher yields with a reduced environmental impact. In this mini-review, we shed light on the literature surrounding the synthesis of Biginelli adducts using MWI and highlight how this heating method can significantly enhance the preparation of this important class of bioactive compounds. By exploring the benefits of MWI, we aim to contribute to the advancement of greener and more efficient synthetic routes for bioactive substances.

Microwave radiation has been utilised since the late 1970s as an alternative thermal energy source for chemical reactions. Initially used in inorganic chemistry, its potential for organic chemistry was revealed in 1986. Convertion of electromagnetic energy into heat, with frequencies ranging from 0.3-300 GHz using microwave irradiation, is an efficient heating method. The microwave heating method has significant potential for industrial processes, reducing reaction times and enhancing yields and selectivity. It finds applications in peptide and organic synthesis, materials science, polymer chemistry, biochemical processes, and nanotechnology. Microwave-assisted organic synthesis is environmentally friendly and beneficial for producing bioactive heterocyclic compounds. Oxygen-containing heterocycles are abundant and possess various biological functions, making them essential for developing new drugs. Microwave technology facilitates the synthesis of these compounds, including bioactive six-membered o-heterocycles such as pyrones, oxazolones, furanones, oxetanes, oxazolidinones, and dioxetanes. By utilizing modern organic transformations, microwave-assisted chemistry enhances the efficiency of synthetic processes, leading to the discovery of more beneficial molecules. The review provides an up-to-date analysis of the synthesis and medicinal properties of O-heterocycles, emphasizing the strengths and needs of this field. It guides researchers, facilitating microwave-assisted green synthesis reactions and offering a flexible platform for forming bioactive heterocyclic rings.

This study incorporates the assembly of development methodologies of microwave-activated protocol involving transition metal catalysts for the synthesis of numerous biologically important heterocycles during the past few years. Herein, it highlights the potential of transition metal salts as catalysts in multicomponent reactions performed under microwave conditions for the formation of oxygen, nitrogen, and sulphur-containing bioactive heterocycle moieties. Microwaveactivated organic synthesis has been well-utilized as an alternative to conventional methodology in pharmaceutical companies due to its potential to significantly improve the rate and consequently diminish the time span of the synthetic process. The traditional methods involving transition metal catalysts for synthesizing bioactive heterocyclic molecules are prolonged and, thus, difficult to meet the requirements for the timely supply of these important compounds. In our review, our main focus is on integrating such synthetic strategies involving transition metal catalysis with a microwaveactivated multicomponent approach for developing bioactive heterocycles.

One of the most efficient non-conventional heating methods is microwave irradiation. In organic synthesis, microwave irradiation has become a popular heating technique as it enhances product yields and purities, reduces reaction time from hours to minutes, and decreases unwanted side reactions. Microwave-assisted organic synthesis utilizes dielectric volumetric heating as an alternative activation method, which results in rapid and more selective transformations because of the uniform heat distribution. Heterocyclic compounds have a profound role in the drug discovery and development process along with their applications as agrochemicals, fungicides, herbicides, etc., making them the most prevalent form of biologically relevant molecules. Hence, enormous efforts have been made to flourish green routes for their high-yielding synthesis under microwave irradiation as a sustainable tool. Among the different clinical applications, heterocyclic compounds have received considerable attention as anti-cancer agents. Heterocyclic moieties have always been core parts of the development of anti-cancer drugs, including market-selling drugs, i.e., 5-fluorouracil, doxorubicin, methotrexate, daunorubicin, etc., and natural alkaloids, such as vinblastine and vincristine. In this review, we focus on the developments in the microwave-assisted synthesis of heterocycles and the anti-cancer activities of particular heterocycles.

One of the most efficient non-conventional heating methods is microwave irradiation. In organic synthesis, microwave irradiation has become a popular heating technique as it enhances product yields and purities, reduces reaction time from hours to minutes, and decreases unwanted side reactions. Microwave-assisted organic synthesis utilizes dielectric volumetric heating as an alternative activation method, which results in rapid and more selective transformations because of the uniform heat distribution. Heterocyclic compounds have a profound role in the drug discovery and development process along with their applications as agrochemicals, fungicides, herbicides, etc., making them the most prevalent form of biologically relevant molecules. Hence, enormous efforts have been made to flourish green routes for their high-yielding synthesis under microwave irradiation as a sustainable tool. Among the different clinical applications, heterocyclic compounds have received considerable attention as anti-cancer agents. Heterocyclic moieties have always been core parts of the development of anti-cancer drugs, including market-selling drugs, i.e., 5-fluorouracil, doxorubicin, methotrexate, daunorubicin, etc., and natural alkaloids, such as vinblastine and vincristine. In this review, we focus on the developments in the microwave-assisted synthesis of heterocycles and the anti-cancer activities of particular heterocycles.

Peptides are important as drugs and biologically active molecules. The synthesis of peptides has gathered considerable attention in recent years due to their various attractive properties. Conventional peptide synthesis is tedious and requires hazardous reagents and solvents. Microwave- assisted solid-phase peptide synthesis has several advantages compared with conventional batch synthesis. Herein, we have discussed various microwave-assisted solid-phase peptide bond synthesis methods developed over the last five years. Peptides are categorized into four groups - small, medium, large, and cyclic based on their length and structural characteristics to make it easier to understand. This review article also discusses the scope and limitations of microwave-assisted solid-phase peptide synthesis.

Microwave-assisted synthesis is a powerful tool in organic chemistry, providing a rapid and efficient method for the synthesis of bioactive heterocycles. The application of microwaves significantly reduces reaction times and increases percentage yields with high purity of the final product. To make the synthetic protocol greener, the application of the magnetic nanocatalyst is a rapidly growing area of interest nowadays. Magnetic nanocatalyst, with its unique features like magnetic separable facile recovery from the reaction media heterogeneously, makes the overall synthetic strategy cleaner, faster, and cost-effective. Aiming this, in the present review, we will focus on the infusion of Magnetic nanocatalyst to microwave-assisted synthesis of various classes of azaheterocyclic compounds, including pyridines, pyrimidines, quinolines, and benzimidazoles. The synthetic methodologies involved in the preparation of these heterocycles are highlighted, along with their biological activities. Furthermore, in this review, the most recent and advanced strategies to incorporate nanocatalysts in the microwave-assisted synthesis of natural products containing azaheterocyclic moieties in drug discovery programs are elucidated in detail, along with the incoming future scope and challenges.

The microwave chemistry of several bioactive natural products and synthetic compounds was studied by us. The compounds of different types, such as alkaloid, terpenoid, lignan, etc. were considered for our investigation. Some indole compounds, as well as organosulfur and miscellaneous carbonyl compounds, were also included. The substrates were irradiated under microwave irradiation for a short time and the resulting products were characterized. The conversion was conducted without using any solvent. The catalysts were not required in many transformations, but in some cases, catalysts, mainly heterogeneous catalysts were needed. The experimental procedures were convenient, less expensive, and generally eco-friendly. The interesting results of our efforts are briefly discussed in the present article.

Background: Tuberculosis is an effectual infectious disease caused by the spread of tubercular bacteria within the lungs via droplets of coughs and sneezes. In 2021, 1.6 million people died due totuberculosis, which is the 13th leading killer disease and 2nd leading after COVID-19 infectious disease.Objective: Many drugs are available as antitubercular drug, but still, requires more efficacious drug molecules with lower toxicity, side effects and small-sized molecules. To fulfill said prospective, computational study such as molecular docking and ADMET studies guides towards an ideal drug molecule with small -sized, unique spiro structures.Methods: Conventional and microwave-initiated Reaction of cyclohexanone, hydrazine carbothioamide, and 2-amino-4-methoxy-6-methyl-1,3,5-triazine affords compound 1, which is subjected to the Schiff base reaction with diverse aldehydes. All structures are defined using IR, 1H NMR, 13C NMR, and mass spectroscopy. The entire series is exposed to in vitro antibacterial and antitubercular and in silico molecular docking and ADMET studies.Results: Compounds 2c and 2b have been established to be potential antibacterial agents, whereas compounds 2d, 2e, 2j, 2k and 2l are extremely effective against tubercular strains. Furthermore, molecular docking of related molecules is performed, and compounds 2d, 2e, 2j, 2k, and 2l have higher affinities toward antitubercular proteins. ADMET parameters such as water solubility, SA score, PCaco2 value, and TPSA values are satisfactory.Conclusion: The microwave method has been proven to be a greener method as compared to the conventional heating method. Comparative results of in vitro analysis are obtained with referenced antibacterial drugs and antitubercular drugs. In silico observations supports their in vitro assessments. Appraisal obtained from the ADMET study leads to the formation of ideal drug molecules.

Aim: This is a comparative study of some new coumarin substituted thioaryl pyrazolyl pyrazoline.Methods: The target compounds were synthesized using both conventional as well as microwave irradiation by reaction of coumarin chalcones with different substituted hydrazine hydrates and aryl hydrazines to give the resultant pyrazoline derivatives. Microwave reaction, enhanced organic reactions, and reduced reaction time led to better yields and selectivity than conventional methods.Results: The obtained compounds were characterized by different spectroscopic analysis including IR, 1H-NMR, 13C-NMR, mass spectroscopy and elemental-analysis and evaluated for their antimicrobial screening against a representative panel of bacteria (Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Salmonella typhi) and fungi (Aspergillus niger, Candida albicans).Conclusion: In the present study, we have synthesized coumarin pyrazoline derivatives clubbed with benzofuran pyrazole via both conventional and microwave irradiation and also subjected to antibacterial and antifungal studies. Synthesis of target compounds by the microwave irradiation enhanced reaction rate and reduced reaction time led to better yields and selectivity than conventional methods. The study of antibacterial and antifungal activities revealed that all the compounds exhibited reasonable to excellent activities against the pathogenic strains.

Lignin is a very abundant biopolymer with great potential to produce other high-value polymers with aromatic groups. Its valorization has been limited principally by its poor solubility in conventional organic solvents, which makes it difficult to deconstruct or transform it into other products with higher added value. In this work, we describe a one-pot procedure to prepare various Deep Eutectic Solvents and study their ability to dissolve Kraft lignin with the aid of microwave dielectric heating efficiently.Background: Lignin is a widely available aromatic biopolymer that is largely discarded or used as a low-value fuel when separated in paper production processes, so researchers are engaged in the development of lignin dissolution processes that allow its easy deconstruction and transformation into other products with higher added value.Objective: The main objective of this work is to find deep eutectic solvents capable of dissolving significant quantities of lignin with the aid of microwaves as a heating source.Method: The present work developed a simple, fast, and efficient method to dissolve lignin using Deep Eutectic Solvent/acetonitrile as solvents and irradiation by dielectric microwave heating.Results: Most of the DESs studied achieved significant dissolution of purchased lignin with common organic solvents by employing microwave irradiation as the heating method.Conclusion: Some DESs studied in this work are good alternatives as solvents for lignin solvent option of simple preparation from renewable precursors from biomass, such as glycerol, choline chloride, and urea, of low toxicity and cost for this application. The effectiveness of these systems appears to be based on molecular recognition by hydrogen bonding interactions involving the three species that make up the eutectic and the hydroxyl groups of the lignin. These solvents can be recovered and recycled.

Background: The characteristics of matter and the dynamics of molecular processes are examined by acoustic approaches. The primary techniques in molecular acoustics are the measurement of sound speed and sound absorption, as well as the relationship between these quantities and different physical variables including pressure, temperature, and wave frequency. Molecular acoustics emerged as a separate field in the 1930s. When it was discovered that many substances disperse the speed of sound during the transmission of sound waves through them and that the classical law, which states that the coefficient of absorption is proportional to the square of the frequency, however, it does not adequately describe how sound is absorbed.Objective: The ultrasonic technique is employed because it is one of the most popular techniques, which is very easy to use, and provides precise velocity results. With careful analysis of the results, the correlation between solute and solvent was discovered. In the pharmaceutical, agricultural, and cosmetics industries, dextran and its derivatives from a few select strains have found a wide range of uses. This is why we have chosen it for our study. For assessing the impact of temperature and concentration on the aqueous medium containing the polymer dextran, ultrasonic properties are crucial. Pycnometer, Ostwald viscometer, and ultrasonic interferometer were used respectively to measure density (ρ), viscosity (η), and ultrasonic speed (u) at "303 K, 308 K, 313 K, 318 K, and 323 K." The experimental parameters are used to determine the acoustic parameters "adiabatic compressibility, Intermolecular free length, relaxation time, acoustic impedance, and Gibb's free energy".Methods: To measure the density, viscosity, and ultrasonic velocity of the solution using a pycnometer, an Ostwald's viscometer, and an ultrasonic interferometer, and to calculate the thermo acoustical parameters based on the measured parameters.Results: Applications for examining the physico-chemical behaviour of aqueous dextran using ultrasound include understanding the nature of molecular interactions.Conclusion: It was investigated how concentration and temperature affected the thermoacoustic characteristics of aqueous dextran. Hydrogen bonds, charge transfer complexes, and the dissolution of hydrogen bonds and complexes are only a few examples of the forces that exist between molecules and how the analysis has interpreted their nature. Weak intermolecular forces exist.Other: Recent developments in ultrasonic techniques have made them an effective tool for evaluating information regarding the physical and chemical behaviour of liquid molecules.