Green synthetic protocol refers to the development of processes for the sustainable production of chemicals and materials. For the synthesis of various biologically active compounds, energy-efficient and environmentally benign processes are applied, such as microwave irradiation technology, ultrasound-mediated synthesis, photo-catalysis (ultraviolet, visible and infrared irradiation), molecular sieving, grinding and milling techniques, etc. Thesemethods are considered sustainable technology and become valuable green protocol to synthesize new drug molecules as theyprovidenumerous benefits over conventional synthetic methods.Based on this concept, oxadiazole derivatives are synthesized under microwave irradiation technique to reduce the formation of byproduct so that the product yield can be increased quantitatively in less reaction time. Hence, the synthesis of drug molecules under microwave irradiation follows a green chemistry approach that employs a set of principles to minimize or remove the utilization and production of hazardous toxic materials during the design, manufacture and application of chemical substances.This approach plays a major role in controlling environmental pollution by utilizing safer solvents, catalysts, suitable reaction conditions and thereby increases the atom economy and energy efficiency. Oxadiazole is a five-membered heterocyclic compound that possesses one oxygen and two nitrogen atoms in the ring system.Oxadiazole moiety is drawing considerable interest for the development of new drug candidates with potential therapeutic activities including antibacterial, antifungal, antiviral, anticonvulsant, anticancer, antimalarial, antitubercular, anti-asthmatic, antidepressant, antidiabetic, antioxidant, antiparkinsonian, analgesic and antiinflammatory, etc. This review focuses on different synthetic approaches of oxadiazole derivatives under microwave heating method and study of their various biological activities.

Microwave radiation is used as a heating source during the synthesis of heterocyclic compounds. The heating mechanisms involved in microwave-induced synthesis include dipolar polarization and ionic conduction. This heating technology follows the green protocol as it involves the use of recyclable organic solvents during synthesis. The microwave heating approach offers a faster rate of reaction, easier work-up procedure, and higher product yield with purity and also reduces environmental pollution. So, microwave heating is applied as a sustainable technology for the efficient production of pyrimidine compounds as one of the heterocyclic moieties. Pyrimidine is a six-membered nitrogenous heterocyclic compound that plays a significant role due to several therapeutic applications. This moiety acts as an essential building block for generating drug candidates with diverse biological activities, including anti-cancer (capecitabine), anti-thyroid (propylthiouracil), antihistaminic (pemirolast), antimalarial (pyrimethamine), antidiabetic (alloxan), antihypertensive (minoxidil), anti-inflammatory (octotiamine), antifungal (cyprodinil), antibacterial (sulfamethazine), etc. This review is focused on the synthesis of pyrimidine analogs under microwave irradiation technique and the study of their therapeutic potentials.

Microwave-assisted chemical reactions are utilized as an emerging tool in drug synthesis as this technique is simple, economic, and efficient. So, a new series of 1,2,4-triazole derivatives are obtained via multi-component reactions under microwave irradiation. First of all, benzohydrazide was obtained by esterification of benzoyl chloride with methanol in presence of concentrated sulphuric acid followed by reaction with hydrazine hydrate. So, carbon disulfide was added dropwise to benzohydrazide in ethanolic potassium hydroxide solution to yield potassium dithiocarbazinate which was cyclized by reacting with hydrazine hydrate to afford 1,2,4-triazole-3-thiol. Further, various Schiff’s bases were prepared by reacting 1,2,4-triazole-3-thiol with different substituted benzaldehydes under microwave irradiations. The characterization of the newly synthesized triazole derivatives were carried out by spectral studies including FT-IR, 1H-NMR, and LC-MS. The tested compounds exhibited significant in-vitro anthelmintic and antimicrobial activities as compared to the standard drugs.

The synthesis of heterocyclic compounds via carbon-nitrogen (C-N) bond formation reaction is considered as an emerged and efficient protocol in the field of synthetic chemistry. The C–N bond-forming reactions can proceed through condensation, coupling, ring-opening, cyclization or ring closure process etc. The reactivity pattern of these reactions mainly depends upon the reaction conditions as well as the type of catalysts and reacting substances that are associated with the synthesis of heterocyclic compounds containing the C-N system including pyrazole, imidazole, pyridine, pyrimidine, thiazole, tetrazole, isoxazole, benzothiazine and benzimidazole etc. Further, the technique of microwave-induced synthesis becomes an alternative strategy for the sustainable production of structurally diverse organic compounds. This method provides a cleaner reaction, faster reaction rate, atom economy and energy-efficient. So, the utilization of microwave radiation in organic synthesis becomes resource-friendly and eco-friendly processes. It follows the green chemistry approach by using safer solvents, renewable starting materials and green catalysts. The unique feature of this method is to generate various types of bioactive or medicinal agents.

The microwave irradiation method is applied for the efficient synthesis of pyrimidine derivatives. The synthetic protocol involves Knoevenagel condensation followed by Michael addition reaction and cyclization of equimolar quantities of aromatic aldehydes, ethyl cyanoacetate and guanidine in the presence of ethanolic NaOH solution to produce corresponding pyrimidine derivatives. The reaction mixture was allowed to reflux under microwave radiation at power level-2 for 7-12 min. The microwave heating technique offers a cleaner reaction with a shorter reaction time and improved product yield as compared to conventional synthesis. The newly synthesized compounds were characterized by their FT-IR, 1H NMR and LC-MS spectral data. All the synthesized pyrimidine derivatives were evaluated in vitro for their antitubercular activity in vitro by using the luciferase reporter phage (LRP) assay method. The antimycobacterial activity was determined in terms of the percent reduction in the relative light unit (RLU). The test compounds exhibited promising antitubercular activity against Mycobacterium tuberculosis H37Rv and clinical isolates, S, H, R and E resistant M. tuberculosis in comparison with the standard drug (isoniazid).

Background: Green strategy involves the design, synthesis, processing, and use of chemical substances by eliminating the generation of chemical hazards. This approach focuses on atom economy, use of safer solvents or chemicals, consumption of energy, and decomposition of the chemical substances to non-toxic materials which are eco-friendly. Objective: So, the microwave irradiated heating method is considered a green and sustainable technique for the development of novel heterocyclic scaffold-like isoxazole derivatives via chalcones. Isoxazole derivatives play a vital role due to their diverse pharmacological activities such as antibiotic (Sulfamethoxazole, Cloxacillin, Flucloxacillin, Cycloserine), anti-fungal (Drazoxolon), Antirheumatic (Leflunomide), antidepressant (Isocarboxazid), antineoplastic (Acivicin), anticonvulsant (Zonisamide), antipsychotic (Risperidone) and anti-inflammatory drugs (Valdecoxib), etc. Methods: The isoxazole derivatives were synthesized with the help of microwave irradiation that follows green chemistry protocol. Results: The titled compounds were subjected to antiepileptic evaluation to determine their therapeutic potential. Conclusion: The use of microwave radiation enhances the rate of the reaction which leads to high selectivity with improved product yields in comparison with the traditional heating methods. The tested compounds exhibited promising antiepileptic activity as compared to the standard drug (Phenytoin).