Microwave-Assisted Synthesis of Imidazole Derivatives: A Recent Update

Background: Microwave-assisted organic synthesis has been a powerful and expedient tool for quick organic synthesis which has vital advantages such as simplicity in process, cumulative rate of reaction, high reaction yields, and less amount of side product etc. Multicomponent reactions have developed chemical transformations for powerful bond-forming in organic, combinatorial and medicinal chemistry. The spirooxindole system possesses prominent biological properties and played a very vital role as a core structure of many synthetic pharmaceuticals. Isatin and its derivatives are a leading molecule for designing latent bioactive agents. Isatin and its derivatives are used as precursors due to having numerous applications and great biological characteristics. Fused chromenes derivatives have established more attention because of their high potential biological application. Here, we have described a one-pot synthesis of diverse spiro[chromene-4,3’-indoline] derivatives using ZrSiO2 mediated three-component reactions of substituted phenols with isatin and malononitrile. Methods: We have used microwave assisted method for synthesis. We have taken mixture of phenol derivatives, Isatin, Malononitrile, the catalyst, ZrSiO2 (10 mol %) and 5 ml methanol was placed into a 25 mL round bottomed flask. The reaction mixture was irradiated under microwave radiations at 100 °C, 300 W for 3-7 min. The progress of the reaction was monitored by thin layer chromatographic plate. After consumption of all starting materials the mixture was poured into water and then extracted with ethyl acetate. The organic layer was washed with brine and evaporated under reduced pressure. The combined aqueous layer was filtered to recycle the catalyst. Filtered catalyst washed with methanol two or three times to remove the strains and tars, and then dried in an oven. Compounds were isolated by column chromatography, elution gradient 15% Ethyl acetate: hexane as pure yellow solid with 80-90% of yield. The catalyst was reused up to three cycles with slight decrease of catalytic activity. Antibacterial activity of synthesized compound was carried out on Nutrient- agar plates by well-diffusion assay against test culture. Results: The one pot three-component cyclization reaction of phenol derivatives, isatin and malononitrile in the presence of ZrSiO2 (10 mol %) as catalyst in methanol was performed and the reaction was completed in 3-7 minutes by using microwave irradiation to afford 2-amino-2'-oxospiro [chromene-4,3’-indoline]-3-carbonitrile 4a in good yields. First, we optimized catalyst for finding best catalyst in very short reaction time with high yields. Reactions using ZrSiO2 in methanol give desirable yield with 88 % in very short time. A sensible decrease in the product yield was observed only after the third recycle of the catalyst. The structures of all the newly synthesized compounds were confirmed by various spectroscopy techniques. All the synthesized compounds were screened through antibacterial activity. Most of the synthesized compounds found to be active against Gram negative bacteria and Gram positive bacteria. Conclusion: We have presented a series of 2-amino-2'-oxospiro[chromene-4,3'-indoline]-3-carbonitrile derivatives that have been synthesized by microwave assisted reaction by isatin, malononitrile and various phenol derivatives. We have described a facile, one pot, three component, and environmentally benign protocol using ZrSiO2 as a prompt catalyst which can be reused. Most important of all, the synthesized derivatives can be used for the development of new antibacterial drugs because compounds 4f, 4b and 4d exhibited promising activity as compared to streptomycin. Keywords: Isatin, microwave-assisted synthesis, multi-component reactions, spiro compound, ZrSiO2.

This review summarizes environmentally benign approaches for the synthesis of fused N-heterocycles since 2011. It is mainly focused on one-pot, multicomponent protocols for generating fused N-heterocyclic moieties with biological significance in atom-efficient manner. Several attractive and cost-effective approaches such as metal-, catalyst-, and solvent-free methods are discussed in this review. Electrochemical concept as green and environmentally optional strategy to produce fused N-heterocycles is also discussed. Synthesis of natural bioactive compounds like clausine V, glycoborine, and popular commercial drug alprazolam (Xanax) by utilizing such strategy is described.

Novel activation methods such as ultrasonic activation and microwave irradiation are becoming increasingly popular in the green synthesis of ionic liquids and ionic compounds. The use of ionic liquids and ionic compounds is becoming more and more interesting for scientists precisely because of their growth-stimulating activity.The purpose.Synthesisof trimecaine ethyl iodoethanoatewascarried out via N-alkylation in classical conditions and using ultrasonicirradiation and microwave-assisted synthesis. Methodology.Thestructure and functional groups of novel synthesized substanceidentifiedby1H,13C NMRandIR,and growth-stimulating activity tested fortengenotypes of sweet sorghum seeds.Thesynthesis of trimecaine ethyliodoethanoate was carried out via N-alkylation in classical conditions and using microwave radiation and ultrasonic activation. Results.The synthesized ionic compoundswere characterized by IR, 1H and 13C NMR, growth-stimulating activity was tested on ten varieties and hybrids of sweet sorghum seeds. Alternative methods for the synthesis of ultrasonic and MW activation showed a good result in the synthesis of N,N-diethyl-N-ethylethanoate-N-(2-(mesitylamino)-2-oxoethyl)aminium iodide with a higher isolation yield in a shorter time compared to classical conditions. Conclusion.The product with the highest yield is formed under MW irradiation in a short time, while under classical conditions the yield was lower, and the reaction time was longer. The synthesized ionic compound had a better effect on the energy and germination of all types of sweet sorghum seeds compared to the control.

In the present chapter, we have focused on microwave-assisted synthesis of quinoline-based heterocyclic compounds because this technique has gained popularity over nonconventional techniques for the rapid synthesis of products. With the help of this technique, many researchers have accelerated organic synthesis, and since the past couple of years a large number of research papers have appeared in scientific journals. This has proved the utility of microwave-assisted synthesis in various branches of chemistry. Microwave-assisted organic synthesis may be helpful to increase the yield, decrease reaction time and minimize the formation of hazardous by-products. With the help of this technique, solvent-free reactions can be easily carried out for eliminating toxicity and flammability issues, which are the major concerns with the use of classical solvents. Quinoline compounds serve both as biomimetics and as reactive pharmacophores of numerous drugs and are associated with several biological activities. Considering these facts and the several applications of microwave-induced synthesis in organic and pharmaceutical chemistry, in the present chapter, we have exclusively focused on the synthesis of various quinoline-based heterocyclic compounds.

In this study, organic–metal nanocatalyst was synthesized by reacting ferric(ΙΙ) chloride with organic phosphonate ligand. The particle size was controlled with the help of the surfactant. Nanoparticle structure was analyzed using Fourier transform infrared (FT-IR), thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), scanning electron microscopy (SEM), dispersive X-ray (EDX), Brunauer–Emmett–Teller (BET) isotherm and X-ray diffraction (XRD) spectra. Next, its catalytic activity was investigated in the synthesis of heterocyclic compounds (2,4,5-trisubstituted imidazoles derivatives). Under optimal conditions, the products were obtained with good efficiency and short time. Products identification were evaluated using physical data, FT-IR, 1H and 13CNMR analysis. The results show that the new method, namely the use of iron-phosphonate nanostructures, is effective for the synthesis of trisubstituted imidazole derivatives. This method has many advantages such as short reaction time, high yield, solvent free conditions, recyclability of the catalyst, and easy workup.

Synthesis of heterocyclic compounds has constituted a major part of research in medicinal chemistry. In the last two decades, many of the heterocyclic rings were prepared with appreciable yield by using microwave-assisted synthesis. These rings are central core in a heterocyclic compound that offers different pharmacological activities to the needy. In recent times, the majority of the heterocyclic compounds are synthesized by researchers using this technique and satisfied with the quality and quantity of the product obtained from the respective raw materials. But, there is no review concerning about recent preparation of heterocyclic compounds using microwave-assisted synthesis. In the presented study, an attempt had been made to found out the newer heterocyclic compounds using microwave-assisted synthesis and their biological activities. This review emphasizes the two decades of research work on the preparation of heterocyclic compounds by using microwave-assisted synthesis.

Chapter 4 - Microwave-assisted synthesis of metal–organic frameworks

1, 3, 4-oxadiazole derivatives received considerable attention of different research groups, as they have wide variety of biological activities. 1, 3, 4-oxadiazole derivatives exhibited noteworthy anticancer activities. In recent years, microwave-induced organic reactions attained significant attention due to several benefits, such as short reaction time, cost-effectiveness, excellent yield, and ease of work. In view of above in present work, SAR and mechanism of action of 1, 3, 4-oxadiazole derivatives as anticancer agents, reported by different research groups in recent years are summarized. Present review also highlighted the various synthetic approaches for efficient microwave-assisted green synthesis of 1, 3, 4-oxadiazole derivatives.

Microwave radiation and mechanical grinding as new ways for preparation of saponite-like materials

The catalytic efficiency of silver nanoparticles supported on chitosan as a green, robust, and efficient nanocatalyst for the direct synthesis of biologically active compounds, such as: imidazole derivatives as well as pyrazine scaffolds through multi-component reactions strategy, have been demonstrated. In this work, imidazole derivatives were achieved via pseudo four-component reactions by utilization of benzaldehydes, benzils, anilines, and ammonium acetate under solvent-free conditions. Moreover, pyrazine scaffolds were synthesized through a three-component reaction of phenylenediamine derivatives, isocyanides and various ketones in water. The main advantages of this protocol are the reusability of the catalyst, operational simplicity, mild reaction conditions, and high-yielding.

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.

Using CoCl2 and SbCl3 as precursors and NaBH4 as reducing agent, we obtained nano CoSb3 particles of about 10 nm with the assistance of microwave radiation. Different Sb/Co ratio and different microwave radiation time were used to prepare CoSb3. The results show that single CoSb3 phase was synthesized successfully under the condition of Sb/Co ratio with 5:1 and microwave radiation time with 5 min. The samples with microstructure and nanostructure were synthesized respectively by cold isostatic pressing and sintering method, and their thermoelectric properties were studied. Due to its powder preparation method and its small grain size, the sample with nanostructure has lower electrical resistivity and thermal conductivity than the sample with microstructure. The maximum ZT value was found to be 0.11 at 650 K in the sample with nanostructure, which is about 10 times higher than that of the sample with microstructure.

Starting from 4-aminohippuric acid (AHA), two novel series of heterocyclic compounds of pharmaceutical interest have been synthesised by one-pot, multicomponent reactions under microwave conditions. Reaction of AHA with various aldehydes and benzil in (1:1) EtOH/acetic acid in the presence of ammonium acetate yielded 1,2,3,5-tetra-arylated imidazole derivatives, whereas a solvent-free reaction of AHA with various aldehydes and dimedone (2 equiv.) in the presence of p-TSA yielded 4,9-diarylated 1,8-dioxo-decahydroacridine derivatives. These reactions produced good yields in short reaction times with an easy work-up, and purification of products was achieved by simple recrystallisation.

ABSTRACTZinc Oxide is an important and multi-purpose material in various industries due to its particular chemical and physical properties. Discovering a cheap, fast, clean, safe, and easy to use method, to synthesize this oxide nanoparticle has attracted a lot of attention in recent applications. The unique properties of the microwave and its special heating capabilities have yielded desirable outcomes by combining different synthesis methods. In the recent years, the vast majority of studies focus on the microwave-assisted synthesis of zinc oxide nanoparticles. This review article attempts to go over the recent advancements on the synthesis of zinc oxide nanoparticles with the aid of microwave, different morphologies and applications obtained by this method. Various microwave-assisted synthesis methods are classified, including the solution-based methods such as hydrothermal, sol-gel, and combustion methods. Morphology of the nanoparticles can affect the properties, and subsequently, applications of these nanoparticles. On the other hand, there is great diversity of morphological and synthesis conditions of zinc oxide nanoparticles. Thus, categorizing the synthesis techniques and providing features of them, facilitates the selection of appropriate method for designing new hierarchical structures with potential properties for future applications. Also it is endeavored to focus on the formation mechanisms of these methods. Finally, the various morphologies obtained under microwave radiation and their formation mechanisms are discussed and the effective factors in the synthesis are analyzed and presented. The potential and suitable fields of development and progress in the future studies are also proposed.

The synthesis of N-heterocyclic compounds is an important direction because of their diverse biological functions. Recently, there has been remarkable progress in copper-catalyzed cross couplings with inexpensive, readily available, insensitive-to-air and low-toxicity copper catalysts. This review summarizes recent advances in the copper-catalyzed synthesis of N-heterocyclic compounds. 1 Introduction and Background 2 Synthesis of Five-Membered Heterocycles with One Nitrogen Atom 2.1 Pyrrolidine and Pyrrole Derivatives 2.2 Indole Derivatives 2.3 Indolone and Isoindolone Derivatives 2.4 Oxazole, Isoxazole, Benzoxazole and Benzothiazole Derivatives 3 Synthesis of Five-Membered Heterocycles with Two Nitrogen Atoms 3.1 Imidazole Derivatives 3.2 Benzimidazole Derivatives 3.3 Benzimidazolone Derivatives 4 Synthesis of N-Sulfonyltriazoles 5 Synthesis of Six-Membered Heterocycles with One Nitrogen Atom 5.1 Piperidine and Pyridine Derivatives 5.2 Quinoline and Quinolinone Derivatives 5.3 Isoquinoline Derivatives 6 Synthesis of Six-Membered Heterocycles with Two Nitrogen Atoms 6.1 Quinazoline Derivatives 6.2 Quinazolinone Derivatives 7 Synthesis of N-Fused Heterocycles 8 Summary