Multicomponent reactions: advanced tools for sustainable organic synthesis

Active development of nanotechnology and growing demand for nanomaterials, including metal oxide nanoparticles, makes the problem of developing economical and environmentally friendly synthesis methods urgent. Green chemistry and green synthesis methods based on its principles are an effective solution to this problem. These methods can be used to obtain metal oxide nanoparticles with different compositions, structures, sizes with minimal harm to the environment. The variety of green synthesis methods and reagents makes it possible to choose the most cost-effective options for different regions. The review considers modern green chemistry methods used to obtain and stabilize metal oxide nanoparticles: copper, zinc, zirconium, iron, titanium. Their advantages, disadvantages, and possible directions for further development are discussed. In addition, the review describes the properties and practical applications of metal oxide nanoparticles obtained by means of green chemistry methods.

Multicomponent reactions (MCRs) were useful synthetic tools in organic chemistry that allowed for the creation of complexity from easily accessible basic building blocks. Green MCRs provide effective and sustainable routes to the synthesis of chemical diversity when combined with catalytic processes. Recent developments in environmentally friendly multicomponent catalytic reactions based on energy‐saving techniques, renewable catalysts and green solvents are discussed in this study. These strategies, when coupled, improve not just the reaction's efficiency but also some of the green chemistry principles that reduce waste and energy consumption. Real‐world applications and challenges in the domain are examined using relevant examples, such as Biginelli, Ugi and Passerini reactions. Other future areas noted in the review include the development and application of recyclable catalysts in MCRs in the agricultural and pharmaceutical industries. Multicomponent reactions (MCRs) have revolutionized synthetic organic chemistry by allowing huge molecular frameworks to be efficiently constructed from simple, readily available starting components in a single operational step. When combined with catalytic approaches following green chemistry standards, MCRs provide a very sustainable and economical avenue to a wide range of chemical entities. This study reviews recent breakthroughs in multicomponent catalytic processes performed in ecologically friendly settings, with a focus on green solvents, renewable catalysts and energy‐efficient activation approaches. To maintain synthesis efficiency, selectivity, and scalability, the environmental impact is reduced to a minimal. These approaches, which vary from solvent‐free transformations under mechanochemical conditions to aqueous‐phase reactions with biocatalysts, are at the cutting edge of sustainable chemical synthesis. By combining green chemistry concepts into MCRs, synthetic operations are brought in line with worldwide sustainability goals while also improving atom economy and reducing hazardous waste. This paper gives prospective perspectives on the widespread use of green multicomponent reactions in academic and industrial settings, discusses the current state of the field and highlights key strategies.

Objective: Salicylic acid (SA) is a keratinolytic agent also used as preservative in cosmetic products. Green chemistry, known as sustainable chemistry, is the design of products and processes eliminating the use of chemicals. It is applicable throughout a chemical product's life cycle, including its design, manufacture, use, and final disposal. The aim of this study was to synthesize SA with green chemistry methods using different amounts of wintergreen oil and to optimize the relevant steps in this path.Materials and Methods: The SA was synthesized from natural wintergreen oil using green chemistry methods. First laboratory-scale synthesis was developed and 15 laboratory-scale synthesis trial patterns, using reaction temperature, wintergreen oil-sodium hydroxide molar ratio, sodium hydroxide-water weight ratio, reaction time and pH were performed. Purity was analysed with gas chromatography-mass spectrometry (GC-MS) and moisture analysis was performed.Results and Conclusion: As a result of pilot production run with 1 kg, 5 kg, and three batches of 20 kg of wintergreen oil, SA was produced with a yield range of 91.06-93.92 %. The resulting SA batches had a purity of approximately 99%. This is a sufficient degree of purity for SA to be used as a raw material in cosmetics products. Filtering the SA solution using a filter press reduced crystal drying time and brought down the total production time to eight days

Simple SummaryIn the paper, we utilize silver nanoparticles as a catalyst in the degradation of a hazardous dye. The nanoparticles are formed from the simple silver salt by using only a plant extract from a commonly occurring herb. The plant extract contains compounds that can both reduce the silver salt and subsequently cap the surface of the as-prepared particles. There are many environmental advantages to using such an approach—nanoparticles are prepared by using simple green chemistry and the catalytic degradation of dye is carried out by sunlight energy. Such a method can be used as a very cheap, green method to neutralize hazardous substances in-house.Nowadays, nanostructures having tremendous chemical and physical properties are gaining attention in the biomedical industry. However, when they are prepared through classical methods (physical and chemical), they are often non-biocompatible and toxic. Considering the mentioned factors, in this research, organometallic silver nanostructures (OMAgNs) have been prepared by the green chemistry method using the acetone, methanol, and methanol-hexane-based extracts of the medicinally important plant Cichorium intybus. Secondary metabolites from C. intybus can be used as an alternative to synthetic reagents at an industrial scale to manufacture biosafe and economical nanostructures with enhanced physicochemical parameters. Prepared nanostructures were characterized using SEM, XRD, FTIR, TGA, UV, and zeta potential measurement. SEM analysis revealed different shapes of OMAgNs, prepared with various extracts. XRD analysis showed the crystallinity of the nanostructures. FTIR spectroscopy helped to identify groups of compounds present in the extracts and used for the OMAgNs synthesis. Out of the three tested OMAgNs, those prepared with methanol extract were selected due to the highest obtained yield and stability (highest negative zeta potential) and were tested as a cost-efficient and active agent to photodegrade organic pollutant, Brilliant Blue R, using energy from sunlight. A decrease in UV-VIS absorbance confirmed the rapid degradation of the dye.

This review is a compilation of the green synthetic methods used in the synthesis of coumarin derivatives. Coumarins are a class of compounds with a pronounced wide range of biological activities, which have found their application in medicine, pharmacology, cosmetics and food industry. Their biological activity and potential application are highly dependent on their structure. Therefore, many researchers have been performing the synthesis of coumarin derivatives on a daily basis. High demands for their synthesis often result in an increased generation of different waste chemicals. In order to minimize the utilization and generation of toxic organic substances, green synthetic methods are applied in this manner. These methods are getting more attention in the last few decades. Green chemistry methods cover a wide range of methods, including the application of ultrasound and microwaves, ionic liquids and deep eutectic solvents, solvent-free synthesis, mechanosynthesis and multicomponent reactions. All typical condensation reactions for coumarin synthesis like Knoevenagel, Perkin, Kostanecki-Robinson, Pechmann and Reformansky reactions, have been successfully performed using these green synthetic methods. According to the authors mentioned in this review, not only these methods reduce the utilization and generation of toxic chemicals, but they can also enhance the reaction performance in terms of product yields, purity, energy consumption and post-synthetic procedures when compared to the conventional methods. Due to the significance of coumarins as biologically active systems and the recent demands of reducing toxic solvents, catalysts and energy consumption, this review provides a first full literature overview on the application of green synthetic methods in the coumarin synthesis. It covers a literature search over the period from 1995-2019. The importance of this work is its comprehensive literature survey on a specific class of heterocyclic compounds, and those researchers working on the coumarin synthesis can find very useful information on the green synthetic approaches to their synthesis. There are some reviews on the coumarin synthesis, but most of them cover only specific reactions on coumarin synthesis and none of them the whole range of green chemistry methods.

This doctorate was funded by the Regione Emilia Romagna, within a Spinner PhD project coordinated by the University of Parma, and involving the universities of Bologna, Ferrara and Modena. The aim of the project was: - Production of polymorphs, solvates, hydrates and co-crystals of active pharmaceutical ingredients (APIs) and agrochemicals with green chemistry methods; - Optimization of molecular and crystalline forms of APIs and pesticides in relation to activity, bioavailability and patentability. In the last decades, a growing interest in the solid-state properties of drugs in addition to their solution chemistry has blossomed. The achievement of the desired and/or the more stable polymorph during the production process can be a challenge for the industry. The study of crystalline forms could be a valuable step to produce new polymorphs and/or co-crystals with better physical-chemical properties such as solubility, permeability, thermal stability, habit, bulk density, compressibility, friability, hygroscopicity and dissolution rate in order to have potential industrial applications. Selected APIs (active pharmaceutical ingredients) were studied and their relationship between crystal structure and properties investigated, both in the solid state and in solution. Polymorph screening and synthesis of solvates and molecular/ionic co-crystals were performed according to green chemistry principles. Part of this project was developed in collaboration with chemical/pharmaceutical companies such as BASF (Germany) and UCB (Belgium). We focused on on the optimization of conditions and parameters of crystallization processes (additives, concentration, temperature), and on the synthesis and characterization of ionic co-crystals. Moreover, during a four-months research period in the laboratories of Professor Nair Rodriguez-Hormedo (University of Michigan), the stability in aqueous solution at the equilibrium of ionic co-crystals (ICCs) of the API piracetam was investigated, to understand the relationship between their solid-state and solution properties, in view of future design of new crystalline drugs with predefined solid and solution properties.

Chapter 8 - Synthesis of nanostructured materials by green methods

Investigation of electrochemical performance, optical and magnetic properties of NiFe2O4 nanoparticles prepared by a green chemistry method

Improvements in Sustainable Organic Synthesis are usually related to the investigation of less hazardous, non-corrosive and renewable materials, as well as waste prevention, energy efficiency, solvent-free reactions, and the development of efficient reusable catalysts. In this context, multicomponent reactions emerged as important strategies for the rapid and more sustainable synthesis of organic molecules. In addition, the use of task-specific ionic liquids as non-conventional solvents and/or catalysts in multicomponent reactions has recently received great attention, contributing to the development of greener synthetic methodologies. This review describes the studies on the use of structurally diverse homogeneous and heterogeneous sulfonic acid-functionalized task-specific ionic liquids as acidic catalysts for multicomponent reactions applied to the synthesis of nitrogen- and oxygen-based heterocycles, as well as related compounds. The combination of the green credentials of multicomponent reactions and acidic ionic liquids are able to improve process sustainability and green metrics, contributing to sustainable chemical development and, ultimately, to economic growth and cleaner industrial production.

Is 3D printing a good alternative to prepare novel devices for Green Analytical sample preparation?

Green chemistry methods were applied to fabricate a nanoelectrode to capture copper ions for the first time using the new organic reagent (4-(3-(2-(3-nitrophenyl)-4,7-dioxo-1,3-oxazepin-3(2H, 4H, (7H)- yl) thioureido. The ionic double was prepared to manufacture the new copper oxide nanoelectrode from the reaction of the new organic reagent and used it as an organic precipitant with CuO-NP nanoparticles prepared from cinnamon extract using the simple green aqueous method. Several techniques were used (XRD, FTIR, SEM) to characterize these particles. This electrode shows excellent selectivity and sensitivity with a linear range of (10-3 -10-13) M, correlation coefficient (0.9998), electrode life of 77 days, ideal temperatures (30) °C and range Optimum pH (3-9), slope (11.082 mV/decade), limit of detection (9.79×10-13) M. The average crystal size measured by the XRD device was (25) nm. The particles were seen by SEM as spherical. Or almost spherical in shape. UV-Visible spectroscopy, the peak was at wave length at (798) nm. This confirms that nanoparticles have been obtained for Copper material. Functional aggregates were determined by FTIR measurement. Recovery value of (101.1) %. This method was successfully applied to estimate copper ions in polluted water.

The association of antimicrobial compounds with prosthetic adhesives can be considered a promising alternative for users of complete dentures, because, in addition of helping to retain the denture during masticatory forces, it can collaborate in the treatment and/or prevention of prosthetic stomatitis, also in infections in the supporting mucosa caused mainly by the colonization of the fungus Candida albicans on the inner surface of the denture in the form of a biofilm, providing better oral health and quality of life conditions for the edentulous population. In this context, nanotechnology has gained ground in Dentistry, since nanoparticles, especially silver, have antimicrobial potential and prove to be biocompatible and can be used in the treatment of oral infections. Additionally, nanotechnology offers numerous advantages for laboratory studies of compounds with application in health and can become a great ally in the manufacture or improvement of dental materials. Thus, the aim of this study was to evaluate the antimicrobial activity of silver nanoparticles, synthesized by three distinct routes (Ultraviolet light method, Turkevich method and green chemistry method using Glycine max extract), associated with the COREGA powder prosthetic adhesive against the biofilm of C. albicans. For this purpose, thermopolymerizable acrylic resin specimens were made as a substrate (n=3 per group). Afterwards, the surface of the specimens were treated with the association of the denture adhesive and silver nanoparticles, synthesized by the ultraviolet light method (AD + Ag UV group), the Turkevich method (AD + Ag Turk) and the green chemistry method using Glycine max extract (AD + Ag Gm). As controls, specimens were treated with nystatin associated with the patch (AD + Nist group), only the patch (AD group) or were submerged in PBS (PBS group). After the treatments, the biofilm of C. albicans were developed for 3, 6 and 12 hours on the surface of the specimens. Subsequently, analyzes were carried out for antimicrobial activity and fungal cell viability, through the minimum inhibitory and fungicidal concentration, by quantifying the colonyforming units per milliliter, by the colorimetric assay of salts of tetrazolium and confocal laser scanning microscopy. Three independent experiments were carried out and the results were presented as mean standard deviation, considering significant values when p<0.05. After 3, 6 and 12 hours of biofilm development, the groups treated with adhesive and nanoparticles association, regardless of the route, presented a reduced fungal load and a percentage of reduction of biofilm metabolic activity 50% compared to the control groups, and these results were similar and/or better than those obtained with the treatment control group AD + Nist. It was concluded that silver nanoparticles synthesized by UV light, Turkevich method and by the green synthesis through Glycine max extract have excellent antimicrobial activity against Candida albicans biofilms. The combination of silver nanoparticles with COREGA adhesive is an innovative alternative that can have a potential preventive effect for denture stomatitis.

The current research is concerned with the synthesis of magnesium oxide (MgO) nanoparticles (NPs) from Abrus precatorius L. bark extract via the green chemistry method. The synthesized MgO NPs was confirmed by using several characterization methods like XRD, FTIR, SEM, TEM, and UV-visible analysis. The synthesized MgO NPs displayed a small particle size along with a specific surface area. Abrus precatorius bark synthesized MgO NPs with a higher ratio of dye degradation, and antioxidant activity showed a higher percentage of free radical scavenging in synthesized MgO NPs. Zebrafish embryos were used as a model organism to assess the toxicity of the obtained MgO nanoparticles, and the results concluded that the MgO NPs were nontoxic. In addition, the anticancer properties of MgO nanoparticles were analyzed by using a human melanoma cancer cell line (A375) via MTT, XTT, NRU, and LDH assessment. MgO NPs treated a human melanoma cancer cell line and resulted in apoptosis and necrosis based on the concentration, which was confirmed through a genotoxicity assay. Moreover, the molecular mechanisms in necrosis and apoptosis were conferred to depict the association of magnesium oxide nanoparticles with the human melanoma cancer cell line. The current study on MgO NPs showed a broad-scope understanding of the use of these nanoparticles as a medicinal drug for melanoma cancer via its physiological mechanism and also a novel route to obtain MgO NPs by using the green chemistry method.

Doxorubicin functionalized gold nanoparticles: Characterization and activity against human cancer cell lines

The main challenge for achieving better energetic materials is to increase their density. In this paper, cocrystals of HNIW (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane, often referred to as CL-20) with TNT (2,4,6-trinitrotoluene) were synthesized using ethanol in a green chemical method. The cocrystal was formulated as C13H11N15O18 and possesses a higher density (1.934 g cm-3) than published previously (1.846 g cm-3). This high-density cocrystal possesses a new structure, which can be substantiated by the different types of hydrogen bonds. The predominant driving forces that connect HNIW with TNT in the new cocrystal were studied at ambient conditions using single-crystal X-ray diffraction, powder X-ray diffraction, Fourier transform-infrared spectroscopy and Raman spectroscopy. The results reveal that the structure of the new HNIW/TNT cocrystals consists of three one-dimensional hydrogen-bonded chains exploiting the familiar HNIW-TNT multi-component supramolecular structure, in which two hydrogen-bonded chains are between -NO2 (HNIW) and -CH (TNT), and one hydrogen-bonded chain is between -CH (HNIW) and -NO2 (TNT). The changes to the electron binding energy and type of element in the new cocrystal were traced using X-ray photoelectron spectroscopy. Meanwhile, the physicochemical characteristics alter after cocrystallization due to the hydrogen bonding. It was found that the new HNIW/TNT cocrystal is more thermodynamically stable than HNIW. Thermodynamic aspects of new cocrystal decomposition are investigated in order to explain this observation. The detonation velocity of new HNIW/TNT cocrystals is 8631 m s-1, close to that of HNIW, whereas the mechanical sensitivity is lower than HNIW.