Green Reaction Medium Research Articles

Urea-based DES as an amine source to access nitrogen-containing heterocycles

Herein, we report a urea-based DES that acts as an amine source in the synthesis of N-substituted styryl quinazolinone from anthranilic acid via N-acylation, cyclization, and subsequent sp3 CH functionalization under a green reaction medium. The salient features of this approach are gram-scale synthesis, mild reaction conditions, and a metal-free methodology. Additionally, post-functionalization and photophysical properties were evaluated.

Efficient heck and Suzuki-Miyaura cross-coupling reactions catalyzed by heterogeneous Pd NPs-decorated porous MOF catalysts under mild conditions

Carbon-carbon coupling reactions are extremely interesting for a variety of applications, including pharmaceuticals and biologically active compounds. In this study, we investigated the utilization of functionalized MIL-101 porous MOF for stabilizing palladium nanoparticles (NPs) and examined their catalytic performance in the cross-coupling reaction of aryl halides with phenylboronic acid and methyl acrylate under mild conditions. To achieve this, MIL-101(Al) was synthesized using a solvothermal method, followed by functionalization with environmentally friendly l-Cysteine (CYS). Subsequently, the MIL-101(Al)-CYS compound was immersed in an ethanolic solution of palladium and stirred overnight. The catalyst exhibited remarkable efficiency (over 90 %) in Suzuki and Heck cross-coupling reactions, demonstrating excellent activity and recyclability. The reactions were conducted in polyethylene glycol 200 (PEG 200), a green reaction medium, at temperatures of 70 °C and 60 °C, with Pd loadings of 0.22 and 0.08 mol%, respectively. MOF-based catalysts, owing to their highly tunable structures and porosity, hold great promise as heterogeneous catalysts in organic reactions.

BMIM]BF4 Mediated Multi-component Synthesis of Phenyl-4-(1Hpyrazol- 5-yl)-1H-pyrazolo[3,4-b]quinolin-5(4H)-ones and Evaluation of their Anti-cancer Activity

Abstract: Pyrazolo bridged quinolones scaffolds are an important building block in many of the medicinally active new chemical entities. In the current work, synthesis of phenyl-4-(1H-pyrazol-5-yl) conjugated with 1H-pyrazolo[3,4-b]quinolin-5(4H)-ones derivatives has been achieved by one-pot threecomponent reaction of 3-methyl-1-phenyl-1H-pyrazol-5-amine 1, 5,5-dimethylcyclohexane-1,3-diones 2, and 1H-pyrazole-5-carbaldehydes 3 using [BMIM]BF4 as green reaction medium with good yields. Furthermore, the synthesized compounds were evaluated for cytotoxic potential towards HeLa and DU145 cells. Of the eight derivatives, compound 4d exhibited good cytotoxicity with an IC50 value of 8.5 and 8.9 μM against DU145 and HeLa cells, respectively. The molecular docking studies revealed that compound 4d displayed good binding energy (-8.4 kcal/mol) against human checkpoint kinase 1.

Cellulose carbamates via transcarbamoylation/transurethanization of methyl carbamates in superbase-acid conjugate ionic liquids.

A sustainable homogeneous transcarbamoylation/transurethanization protocol for cellulose modification with methyl N-substituted carbamates was developed. The protocol utilizes the superbase ionic liquid [mTBNH][OAc], not only as a green reaction medium, but also as a promotor of the transformation. This approach allows to obtain different cellulose carbamates with controllable degrees of substitution. The solubility of the obtained materials from the newly developed method was compared with the solubility of materials obtained from the isocyanate approach, where some intrinsic trends were observed.

Visible-light-induced C-S bond formation in the synthesis of 2,4-disubstituted thiazoles through cascade difunctionalization of acetophenone: a greener approach.

A groundbreaking approach has been developed for synthesizing 2,4-disubstituted thiazoles using an eco-friendly and metal-free approach. This novel method utilizes methyl aryl ketones, N-bromo-succinimide (NBS), and thioamides in water as a green reaction medium under visible light irradiation. Using NBS as a bromine source, the reaction takes place through an in situ α-bromination method. This approach does not require any catalyst, which makes it exceptionally beneficial for the environment. The advantages of this efficient approach are manifold and include the use of greener conditions, absence of metals, easy isolation of products, cost-effectiveness, non-toxicity, and reliance on renewable energy sources like visible light. Moreover, this technique offers higher product purity and excellent yield, enhancing itsappeal.

Facile synthesis of functionalized quinolinones in a green reaction medium and their photophysical properties

A green, one-pot sequential synthesis of functionalized quinolinones from benzhydrol is reported. This method features mild reaction conditions, high atom economy, scalability, and excellent yields. The photophysical properties were also explored.

Wood modification with trimethoxyphenylsilane via supercritical carbon dioxide for enhanced weathering resistance

Abstract This research focuses on increasing wood resistance against UV degradation using trimethoxyphenylsilane as modifying agent and supercritical CO2 as a green solvent and reaction medium. Trimethoxyphenylsilane was successfully grafted on European spruce (Picea abies, H. Karst) and was characterized by SEM-EDX and UV–vis reflectance. SEM-EDX showed the presence of silicium inside the wood cell wall. Increased wood moisture content showed positive effect on weight gain of trimethoxyphenylsilane after treatment. UV resistance of treated wood was evaluated by following the color change during artificial weathering. Modified samples showed improved weathering resistance compared to unmodified wood with a ΔE value around 5 after 260 h. Processing and modifying wood using supercritical CO2 is a promising route to increase wood performances and increase its use as a building material.

Green Synthesis of Arylideneisoxazol-5-Ones Catalyzed by Silicon Dioxide Nanoparticles

4-Arylideneisoxazol-5(4H)-ones were obtained via a simple and efficient one-pot, three-component cyclocondensation of diverse aldehydes with hydroxylamine hydrochloride and β-keto esters in water. This one-pot heterocyclization has been performed in the presence of catalytic amounts of silicon dioxide nanoparticles (SiO2 NPs) at room temperature. This approach is economical for the synthesis of potentially bioactive 4-arylideneisoxazol-5(4H)-one derivatives. The products were formed in 86–94% isolated reaction yields using 5 mol% nanocatalyst. The heterocyclization reactions were completed at room temperature under aqueous conditions. The significant features of the present procedure are uncomplicated product isolation, purification without chromatographic methods, great biocompatibility of SiO2 NPs, straightforward reaction conditions, easy workup, environmentally friendly, readily available starting materials, reusability of the catalyst, as well as inexpensive and green reaction medium.

Water Mediated Green Method Synthesis of Bioactive Heterocyclic Reported Between 2012-2021 Accelerated by Microwave Irradiation: A Decennary Update

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.

A facile catalyst-free one-pot three component synthesis of pharmacologically important indole-centered 4H-chromenes in a deep eutectic solvent (DES)

Popularity of the multicomponent reactions (MCRs) lies in the versatility as well as simplicity of their synthetic procedures which unlock the access to a variety of valuable bioactive products as well as fine chemicals by means the manifold prospects of the reagent combinations. In this paper, we report a simple, green, and highly efficient protocol to assemble diverse indole-based 4H-chromenes in good yields using a low melting mixture of choline chloride and urea. Herewith, we have employed inexpensive and easily accessible indole derivatives, salicylaldehyde, 2-hydroxy-1-naphthaldehyde, malononitrile, and ethyl cyanoacetate to prepare a variety of indole-centered 4H-chromenes. Importantly, the reaction medium was recycled/reused without any noticeable decrease in both yield as well as the catalytic activity. More importantly, the deep eutectic medium play a dual role, solvent as well as catalyst, and hence avoid the usage of volatile organic solvent and corrosive catalyst, as well. Moreover, we have also revealed the preliminary photophysical (absorption and emission) properties of thus prepared molecules. Since this particular method involve both green reaction medium as well as straightforward catalyst-free multicomponent procedure, it may open up new possibilities to synthesize a wide variety of hybrid indole and chromene based heterocycles of therapeutic uses under green and mild conditions in many years to come.

Microwave-assisted Synthesis of Pharmacologically Active 4-Phenoxyquinolines and their Benzazole-quinoline Hybrids Through SNAr Reaction of 4,7-dichloroquinoline and Phenols Using [bmim][PF6] as a Green Solvent.

Quinoline and its derivatives have been shown to display a wide spectrum of biological properties, especially anticancer activity. Particularly, diverse potent anticancer drugs are based on the 4-phenoxyquinoline skeleton, acting as small-molecules VEGR2 and/or c-Met kinase inhibitors. However, the design of new drugs based on these quinoline derivatives remains a challenge. Up till now, all approaches to 4-phenoxyquinoline skeleton construction do not obey any green chemistry principles. Developing a new, and efficient protocol for the synthesis of potentially bioactive 4-phenoxyquinoline derivatives and benzazole-quinoline-quinoline hybrids from commercially available 4,7-dichloroquinoline and phenol derivatives using microwave energy (MW) in the presence of 1-methyl 3-butylimidazolium hexafluorophosphate. Neweco-efficient protocol for valuable 7-chloro-4-phenoxyquinolines and their hybrids, which is based on SNAr reaction of 4,7-dichloroquinoline with respective simple phenols and hydroxyaryl- benzazoles under MWenergy in green reaction media, is studied for the first time. We found that among various solvents tested, the ionic liquid 1-methyl 3-butylimidazolium hexafluorophosphate ([bmim][PF6]) favored the SNAr reaction affording phenoxyquinolines in excellent yields (72-82%) in 10 min. The developed protocol allowed to obtain quickly in good yields (48-60%) new diverse benzazole-quinoline hybrids, which are expected to be pharmacologically active. According to the calculated bioactivity scores, new hybrids are potential kinase inhibitors that could be useful in anticancer drug research. We developed for the first time a new green, efficient method to prepare potentially bioactive functionalized 7-chloro-4-phenoxyquinolines and benzazole-quinoline molecules. Good to excellent yields of the quinoline products, use of MW irradiation in ([bmim] [PF6] as a green solvent, and short times of reactions are some of the main advantages of this new protocol.

Green fabrication of nanostructured Ni(OH)2/Ni/Carbon felt electrodes with water-containing deep eutectic solvent for enhanced water electrolysis performance

To produce green hydrogen, the development of high-performance, environmentally friendly, and cost-effective electrocatalysts for efficient hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is imperative. This study explores the potential application of water-containing deep eutectic solvents (DESs) in the synthesis of nanostructured electrocatalysts for water electrolysis. Ni(OH)2/Ni/carbon felt (CF) composite electrodes are developed via one-step electrodeposition in a water-containing choline chloride/urea DES as a green reaction medium. Heterostructured Ni(OH)2/Ni nanosheets are formed and uniformly deposited on the CF substrate with the addition of 10 wt% water to DES (CU10W), which increases active sites for HER and OER. The initial confinement of water molecules by the DES is found to be crucial in forming the hierarchical structure of the electrocatalysts. Notably, the CU10W electrode exhibits excellent bifunctional activity toward HER and OER, with reduced overpotentials of 192 and 564 mV, respectively, at 100 mA cm−2. This renders the CU10W electrode-based electrolysis system stable with a reduced cell voltage of 1.69 V and a high Faradaic efficiency of over 99% for the HER. The augmented electrochemical active surface area and reduced charge transfer resistance of the CU10W electrode account for the improved HER/OER performance associated with the special hierarchical Ni(OH)2/Ni nanostructure.

Cucurbit[n]uril synthesis using ethan-1, 2-diyl bis (hydrogen sulfate): A greener reaction medium

Inevitable use of strong mineral acids and limitations to their reusability is one of the major challenges associated with Cucurbit[n]uril (CB[n]) synthesis. Cucurbituril formation does not take place at acid concentrations less than 5 M [1]. Herein, we report an environmentally benign synthesis of cucurbit[n]urils using [ethan-1,2-diyl bis(hydrogen sulfate)] (EDSA) as a green reaction media. The merits of this protocol highlight easy method of catalyst preparation, safe handling and ready recyclability for at least three times and high purity of cucurbituril can be obtained. The reaction can also be carried out in kg scale. These advantages may rank ethane-1,2-diyl bis(hydrogen sulfate) as a catalyst of first choice for cucurbituril synthesis.

Selective aerobic oxidation of biomass model compound veratryl alcohol catalyzed by air-stable copper(ii) complexes in water

Three new copper(ii) complexes were synthesized and successfully utilized as effective catalysts for the selective aerobic oxidation of biomass derived veratryl alcohol to veratraldehyde in water as a green and sustainable reaction medium.

SYNTHETIC APPROACHES OF BENZIMIDAZOLE DERIVATIVES: A REVIEW

Benzimidazole is considered a privileged moiety for the development of molecules with therapeutic potential. Over the years several drugs viz: albendazole, pantoprazole, astemizole, telmisartan, thiabendazole, and benomyl have been developed by optimizing benzimidazole-based structures. Given the various pharmacological implications of benzimidazoles, it encourages to explore new synthetic protocols for benzimidazoles. The review presented here highlights exclusively the recent synthetic approaches to prepare benzimidazole derivatives. Numerous search engines like Science Direct, Semantic Scholar, Scopus, PubMed, and Google Scholar were utilized to collect the data. It was found that benzimidazoles were synthesized in an eco-friendly manner by employing a green reaction medium or reagent with improved yields and efficiency. Various precursors such as o-phenylene diamines, 2-nitroaniline, aniline, o-anilinic amidines, and o-aminoaryl ketone were utilized to obtain the benzimidazole. This work will provide support to synthesize numerous benzimidazole compounds in a convenient and eco-friendly manner.

Highly Efficient Microwave-Assisted Synthesis of 2-Arylimidazo[1,2-a]Pyridine-3-Carbaldehydes in PEG-400

We have designed a simple and efficient method for the synthesis of 2-Arylimidazo[1,2-a]pyridine-3-carbaldehyde from imidazo[1,2-a]pyridines with a mixture of DMF and POCl3 in presence of PEG-400 as a green reaction medium under microwave irradiation at 400 watt, and 90 0C. The main advantages of this protocol compared to other previously developed methods, were its mild reaction condition, high yield percentage, short reaction time, clean reaction profile, and avoidance of toxic catalysts, hazardous organic solvents, and waste production.

Acetic Acid-Water Mediated Efficient One-Pot Synthesis of Functionalized Isoxazolyl Amino Chromeno[4,3-b]pyridine Derivatives

A simple, efficient, economical and environmentally benign method has been developed for one-pot three component synthesis of isoxazolyl amino chromeno[4,3-b]pyridine derivatives from 4-amino-3-methyl-5-styrylisoxazoles, malononitrile and (E)-3-benzylidenechroman-4-one by using acetic acid (AcOH) as a promoter and water as a green reaction medium under thermal condition. The interesting features of this method are environmental friendly, metal-free, less reaction time, wide substrate scope, operational simplicity, easy purification of products and good yields.

Convenient and highly efficient microwave-assisted synthesis of 2-Arylimidazo[1,2-a]pyrimidine-3-carbaldehydes in glycerol

A simple and highly efficient method adopted for the synthesis of 2-Arylimidazo[1,2-a]pyrimidine-3-carbaldehyde from reaction of 2-phenylimidazo[1,2-a]pyrimidines, with (Vilsmeier–Haack reagent) in the presence of glycerol as a green reaction medium under microwave irradiation at 400 watt, at 90 °C. Mild reaction conditions, high yield, short reaction time, a clean reaction profile, avoiding toxic catalysts, hazardous organic solvents, and less waste materials are the advantages over the previously adopted method.

Polystyrene stabilized Pd-Au nanoalloy for efficient synthesis of bis(indolyl)methanes from aryl iodides using oxalic acid as CO and H2 source

Herein, first example of heterogeneously catalyzed carbonylative synthesis of bis(indolyl)methanes from aryl iodides in one-pot and single-step manner has been reported. The reaction was best catalyzed by polystyrene supported bimetallic Pd-Au (Pd-Au@PS) nanoparticles (NPs) in comparison to various supported monometallic Pd-catalysts. The key feature of this protocol involves the application of oxalic acid as economic, solid, and safe multi-functional reagent which acts as a CO, H2 source as well as acid co-catalyst with PEG-200 as green solvent reaction medium for delivering moderate to excellent yields of the desired products, bis(indolyl)methanes (BIMs). The developed protocol is additive, phosphine ligand-free under air/moisture stable recyclable catalyst bearing easy accessibility/affordability to starting materials.

PEG-mediated synthesis, antibacterial, antifungal and antioxidant studies of some new 1,3,5-trisubstituted 2-pyrazolines.

A new series of 1,3,5-trisubstituted 2-pyrazoline derivatives (3a-l) are synthesized in good to excellent yields from the corresponding chalcones (1a-h) and acid hydrazides (2a-e) in polyethylene glycol-400 (PEG-400) as a green reaction medium. The newly synthesized 2-pyrazoline derivatives are screened for their antibacterial and antifungal activity. The synthesized trisubstituted pyrazolines displayed moderate to good antibacterial and antifungal properties as compared with the standard reference penicillin and fluconazole drugs. Additionally, the antioxidant potential of the 1,3,5-trisubstituted 2-pyrazolines is evaluated by OH and DPPH assay. The 1,3,5-trisubstituted 2-pyrazolines showed good radical scavenger activity and were found as good antioxidant agents.