Green Protocol Research Articles

Green Protocol For Synthesis of Cu2O@g‐C3N4 Photocatalysts For 1, 4 Radical Oxidative Addition of Trans Crotonaldehyde Under Visible Light Condition

AbstractUsing visible light conditions, we have developed a green protocol to prepare copper oxide‐doped graphitic carbon nitride (Cu2O@g‐C3N4) photocatalysts with varied ratios of g‐C3N4 nanosheets to copper oxide‐dopant (0.1 %, 0.5 %, 0.7 %, and 5 % respectively) and characterized through various physicochemical techniques. These photo‐responsive catalysts were used for the 1,4 radical oxidative addition of trans crotonaldehyde into β‐hydroxybutyric acid (BA) as a major product, utilizing 30 % hydrogen peroxide as an oxidant and a white LED (Light Emitting Diode) source. Under the innoculous eco‐friendly stipulations, Cu2O@g‐C3N4 (5 %) exclusively promoted the aforementioned reaction leading to 99.85 % trans crotonaldehyde conversion with 66.57 %, 24.1 %, and 9.1 % selectivity for β‐hydroxybutyric acid, crotonic acid and subsequent radical synthesis, respectively.

Tandem Synthesis of Piriqualone and Analogues Using Deep Eutectic Solvents: Photophysical and Theoretical Insights

This study presents a sustainable chemical approach for the tandem synthesis of Piriqualone a sedative and anxiolytic drug and its analogues using a green protocol. The research investigates the ability of deep eutectic solvents (DESs) to act as catalysts as well as solvent in a tandem reaction involving metal‐free dehydrogenation and sp3 C‐H bond functionalization, leading to the formation of styryl‐heterocyclic compounds (7a‐p). These styryl derivatives were thoroughly characterized through spectral analysis and photophysical property evaluation. The relationship between chemical structure and AIE properties was particularly examined for compound 7n. Additionally, the experimental findings were corroborated by density functional theory (DFT) calculations. The structures of compounds 7j, 7p and 7fa were further validated through single crystal X‐ray diffraction (XRD) analysis.

Green Protocol for the Synthesis of Luminescent Carbon Nanodots Derived from Murraya Koenigii Leaves and Urea: Enhancing Photoluminescence for Advanced Bioimaging.

We have synthesized Murraya Koenigii leaves powder-derived carbon nanodots (CNDs) by hydrothermal method. A tribute to our commitment to environmental sustainability is the unique composition of our CNDs, which are made entirely of natural carbon sources and a green solvent, water. Our further efforts to improve performance led us to start making nitrogen-doped CNDs. By using urea as a non-toxic source of nitrogen, we observed a substantial increase in fluorescence intensity, extending the usefulness and potential of these nanomaterials. We investigated the optical properties using UV-Vis and fluorescence spectroscopy. The other parameters, like structural and size-shape morphology, were analyzed using FTIR, XRD, and HR-TEM, respectively. The fluorescence spectroscopy demonstrated their capability to exhibit wavelength-dependent photoluminescence (PL), highlighting the potential of these CNDs for cell bioimaging applications. The fluorescence properties affirm their suitability for biomedical applications, as they do not involve any inherent risk to cells.

Synthesis of SCD3-containing bicyclo[1.1.1]pentanes enabled by photocatalyzed difunctionalization of [1.1.1]propellane

Bicyclo[1.1.1]pentanes (BCPs) have emerged as appealing bioisosteres for para-substituted benzene rings in drug design. In this study, we report an intermolecular photocatalytic addition of [1.1.1]propellane and S-(methyl-d3) arylsulfonothioates to synthesize novel deuterium-containing BCPs derivatives via energy transfer processes (EnT). This efficient and green protocol provides an access to introduce deuterium into BCP scaffolds and enriches the present library of BCPs compounds for drug design.

Microwave‐Assisted, Multicomponent Synthesis of Pyrazolo [3, 4‐b] Pyridines Under Green Conditions

AbstractDeveloping novel and environmentally friendly green methodologies are critical in synthetic organic chemistry. Here, we investigated the one‐pot, efficient green synthesis of pyrazolo[3,4‐b]pyridine derivatives via a multicomponent approach. The reactions were operated in an aqueous medium by using microwave irradiation and conventional protocols. The green protocol offered high yields of desired product in swift reaction time, and good tolerance under reaction conditions.

Rethinking Nanoparticle Synthesis: A Sustainable Approach vs. Traditional Methods.

This review portrays a comparison between green protocols and conventional nanoparticle (NP) synthesis strategies, highlighting each method's advantages and limitations. Various top-down and bottom-up methods in NP synthesis are described in detail. The green chemistry principles are emphasized for designing safe processes for nanomaterial synthesis. Among the green biogenic sources plant extracts, vitamins, enzymes, polysaccharides, fungi (Molds and mushrooms), bacteria, yeast, algae, and lichens are discussed. Limitations in the reproducibility of green protocols in terms of availability of raw material, variation in synthetic protocol, and selection of material due to geographical differences are elaborated. Finally, a conclusion is drawn utilizing green chemical principles, & a circular economy strategy to minimize waste generation, offering a promising framework for the synthesis of NPs emphasizing sustainability.

Mangrove tree aerial root extract mediated green synthesis of Ag/Fe3O4/rGO nanocomposite and its application as a catalyst for one potsynthesis of 7-phenyl-6H,7H-benzo[4,5]imidazo[2,1-b]chromeno[4,3-d][1,3]thiazin-6-one derivatives.

In this study, we report the green preparation of magnetically separable Ag/Fe3O4/rGO nanocomposites using mangrove tree aerial root extract as a stabilising agent. The morphology, size, chemical composition, magnetic property and other characteristic parameters of synthesised Ag/Fe3O4/rGO nanocomposite were determined by analytical techniques like Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM),transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). The results proved that mangrove tree aerial root extract has the ability to reduce Ag+ ions, graphene oxide (GO) to Ag nanoparticle and reduced graphene oxide (rGO), respectively. The prepared Ag/Fe3O4/rGO nanocomposite was used successfully as a prompt catalyst for synthesis of 7-phenyl-6H,7H-benzo[4,5]imidazo[2,1-b]chromeno[4,3-d][1,3]thiazin-6-one derivatives by one-pot multi-component reaction of 4-hydroxycoumarin (10mmol), 2-mercaptobenzimidazole (10mmol) and different arylaldehyde (10mmol) in the presence of ethanol (10ml) as an eco-benign solvent at reflux condition. By utilising this protocol, we have constructed 7-phenyl-6H,7H-benzo[4,5]imidazo[2,1-b]chromeno[4,3-d][1,3]thiazin-6-one derivatives in good to excellent yield of 80-90%. This synthesis involves the formation of C-C, C-N and C-S bonds. The synthesised organic heterocyclic compounds were examined for the green matrix properties such as atom economy (AE), E-factor and product mass intensity (PMI). This green protocol is of big interest due to employing simple, non-toxic heterogeneous, separable, reusable Ag/Fe3O4/rGO as an eco-safe heterogeneous catalyst and environmentally benign ethanol as a green solvent without the use of any harmful mineral acid and toxic transition metal catalyst.

Rapid Synthesis of Schiff Bases via Pyridine‐2‐Carboxylic Acid as an Effective Catalyst

AbstractThis work focuses on the rapid synthesis of Schiff bases with green protocols, where P2CA (Pyridine‐2‐carboxylic acid) is utilized as a catalyst. The condensation reaction of aldehydes and anilines, facilitated by P2CA, resulted in the production of Schiff bases in good to excellent yield within a remarkably short time of up to 15 min. The electronic effect of the various substituents on aldehyde and aniline, in combination with the catalytic effect of P2CA, accelerated the reactions under mild conditions. The reusability of the catalyst was thoroughly examined, and the catalyst was characterized over every cycle. Importantly, this approach is not only green and sustainable, but also cost‐effective, harmless, and environmentally friendly, thanks to the affordability and benign nature of P2CA.

Water-based synthesis of dextran-methacrylate and its use to design hydrogels for biomedical applications

Polysaccharide-based hydrogels are desirable for biomedical applications owing to their biocompatibility and physicochemical tunability. The chemical modification of polysaccharides with photo-sensitive groups, such as methacrylates is a common method to obtain new hydrogel materials. This study introduces a non-toxic water-based method to effectively functionalize dextran with methacrylate groups. The methacrylation reaction with methacrylic anhydride in water in the presence of NaOH was rapid and efficient (85 % − 92 % yield), permitting degrees of substitution (DS) up to 62 % within 60 min. An unconventional solid-state photo-crosslinking method was employed to form chemically crosslinked dextran-based hydrogels with LAP (lithium phenyl-2,4,6-trimethylbenzoylphosphinate) as the photoinitiator. By varying the polymer formulations (DS, polymer mass, LAP concentration), a wide range of hydrogels were obtained with various swelling ratios (40–250 %) and release kinetics of model drug and protein biomolecules. Compression modulus values ranged from 32 ± 1 to 342 ± 10 MPa (dry state) and 87 to 8500 kPa (swollen state). Cytotoxicity experiments indicated good biocompatibility for the crosslinked dextran hydrogels. The green synthesis protocols and obtained dextran-based hydrogels with high mechanical strength open up perspectives for applications from tissue engineering to the design of medical devices such as microneedles.

Cydonia oblonga extract mediated biosynthesis of gold nanoparticles: Analysis of its anti-oral cancer and antioxidant properties

Here, using natural and biological macromolecules derived from Cydonia oblonga extract, we have developed a green protocol for the biogenic made Au NPs. Under ultrasonic activated conditions, the Cydonia oblonga phytomolecules were employed as an efficient green reducing agent for the Au3+ ions to the Au0 NPs. Additionally, by encapsulating or capping, they allowed the Au NPs to stabilize on their own. Several physicochemical techniques, such as elemental mapping, TEM, FE-SEM, UV–Vis spectroscopy, EDS, and ICP-OES, were used to analyze the structure of the Au NPs/Cydonia oblonga bio-nanocomposite. The field of medicinal therapeutics pertaining to human health includes cancer treatment as a major component. Subsequently, the as prepared Au NPs/Cydonia oblonga bio-nanocomposite was investigated for antioxidant and human anti-oral cancer assays. In such studies a number of cell lines, viz., HSC-3, HSC-2, and Ca9-22 were used in determining the cytotoxicity. Notably, Au NPs/Cydonia oblonga exhibit significant anti-oral cancer properties against HSC-3, HSC-2, and Ca9-22 cancer cell lines following time and dose-dependent manner. The corresponding IC50 values were determined as 201, 192, and 246 µg/mL respectively. DPPH radical scavenging method was used to determine the antioxidant activity of Au NPs/Cydonia oblonga bio-nanocomposite. The significant IC50 value suggested the material having very good antioxidant potential. The anti-human oral cancer effect of our material is believed to be due to its antioxidant effects.

Development of Thin Film Microextraction with Natural Deep Eutectic Solvents as 'Eutectosorbents' for Preconcentration of Popular Sweeteners and Preservatives from Functional Beverages and Flavoured Waters.

An eco-friendly method for the determination of sweeteners (aspartame, acesulfame-K) and preservatives (benzoic acid, sorbic acid, methylparaben, ethylparaben) in functional beverages and flavoured waters using thin film microextraction (TFME) and high-performance liquid chromatography with UV detection (HPLC-UV) was proposed. A series of fourteen green and renewable solidified natural deep eutectic solvents (NADESs) were prepared and tested as 'eutectosorbents' in TFME for the first time. In the proposed method, the NADES containing acetylcholine chloride and 1-docosanol at a 1:3 molar ratio was finally chosen to coat a support. Four factors, i.e., the mass of the NADES, pH of the samples, extraction time, and desorption time, were tested in the central composite design to select the optimal TFME conditions. Limits of detection were equal to 0.022 µg mL-1 for aspartame, 0.020 µg mL-1 for acesulfame-K, 0.018 µg mL-1 for benzoic acid, 0.026 µg mL-1 for sorbic acid, 0.013 µg mL-1 for methylparaben, and 0.011 µg mL-1 for ethylparaben. Satisfactory extraction recoveries between 82% and 96% were achieved with RSDs lower than 6.1% (intra-day) and 7.4% (inter-day). The proposed 'eutectosorbent' presented good stability that enabled effective extractions for 16 cycles with recovery of at least 77%. The proposed NADES-TFME/HPLC-UV method is highly sensitive and selective. However, the use of a solid NADES as a sorbent, synthesized without by-products, without the need for purification, and with good stability on a support with the possibility of reusability increases the ecological benefit of this method. The greenness aspect of the method was evaluated using the Complex modified Green Analytical Procedure Index protocol and is equal to 84/100.

Application of a new green protocol in solid-phase peptide synthesis: identification of a new green solvent mixture compatible with TBEC/ETT

ABSTRACT Solid Phase Peptide Synthesis (SPPS) is the preferred technique for synthesizing bioactive peptides. However, traditional SPPS generates significant waste and employs hazardous solvents like DMF and DCM. The aim of this research is to investigate solvents and agents of coupling that align with the green chemistry and are suitable for all stages of SPPS. Some solvents, such as p-cymene and anisole, taken into consideration in this work, can be derived from renewable sources like plants and biomass, rendering them environmentally sustainable choices. However, many of these alternative solvents possess different physicochemical properties compared to DMF. To overcome this challenge, solvent mixtures are employed. In this study, we identified a novel green solvent mixture by combining anisole with NOP; its ability to swell different resins and its capability to solubilize all Fmoc protected amino acids was investigated. The same mixture was also assessed with a green coupling agent, TBEC, in combination with ETT as additive. Model peptides Aib-enkephalin and Aib-ACP were synthesized resulting in favorable outcomes in terms of peptide synthesis efficiency, 97.81% and 98.86%, respectively.

Microwave and ultrasound-assisted green protocols for 5-methylthiazole induced Betti bases: molecular docking, in-silico pharmacokinetics, and anticancer activity studies

ABSTRACT Herein, we describe an efficient one-pot three-component microwave and ultrasound-endorsed approaches for synthesizing distinct 5-methylthiazole induced Betti bases (5-methyl-thiazol-2-ylamino-aryl-benzylnapthols) employing silica sulfuric acid (SSA, silica-OSO3H) as an active heterogeneous acid catalyst. The title compounds produced in good yields (86–95%) from naphthalen-2-ol, 5-methylthiazol-2-amine, and assorted aryl aldehydes; and structurally characterized by spectral and elemental analyses. A comprehensive comparative study of conventional, ultrasonic, and microwave-irradiated synthetic routes has been achieved by optimizing various reaction parameters. These new protocols provide several advantages, including the use of an inexpensive, non-toxic, and reusable catalyst. Additionally, they benefit from mild reaction conditions, short reaction times, and simple workup and purification procedures, thereby increasing their practicality. Furthermore, the synthesized compounds were evaluated for their anticancer potency against A-549 (lung cancer) and A-498 (kidney cancer) cell lines, with scaffold IVa demonstrating excellent (GI50 < 10 µg/mL) inhibitory activity against A-549. Additionally, molecular docking was performed to investigate potential binding interactions between ligands and proteins. Scaffold IVa exhibited the best docking with cancerous target proteins 1M17 (−8.9 kcal/mol) and 1M14 (−7.2 kcal/mol), thereby supporting our bio-activity studies.

Methanol‐mediated One‐pot Transformation of Benzonitriles to Five and Six‐Membered Heterocycles: Synthesis and Mechanistic Approach

Herein we describe a facile methodology for the synthesis of heterocyclic molecules such as 2‐aryl‐substituted imidazolines, oxazolines and 1,4,5,6‐tetrahydropyrimidines, under one‐pot and metal‐free conditions. A series of electron‐poor substituted benzonitriles were used as starting materials with different available diamines and amino alcohols, producing the desired products in good to high yields within methanol and in the absence of catalyst or additives. This methodology can be easily scaled up to laboratory size of 3 mmol for both five‐ and six‐membered heterocycles. Detailed mechanistic and theoretical studies supported the dual role of methanolic media as solvent and as mediated agent. To shed light on the reaction mechanism, DFT mechanistic studies suggest a distinction in the first step, with the activation of the nitrile by methanol, and the formation of a benzimidamide and/or a benzimidate (observed by NMR) as intermediates. This facile synthetic procedure provides a green, metal‐free, and mild protocol for the synthesis of a series of imidazoline, oxazoline and tetrahydropyrimidine derivatives

Novel Bioplastic Based on PVA Functionalized with Anthocyanins: Synthesis, Biochemical Properties and Food Applications.

Over the last ten years, researchers' efforts have aimed to replace the classic linear economy model with the circular economy model, favoring green chemical and industrial processes. From this point of view, biologically active molecules, coming from plants, flowers and biomass, are gaining considerable value. In this study, firstly we focus on the development of a green protocol to obtain the purification of anthocyanins from the flower of Callistemon citrinus, based on simulation and on response surface optimization methodology. After that, we utilize them to manufacture and add new properties to bioplastics belonging to class 3, based on modified polyvinyl alcohol (PVA) with increasing amounts from 0.10 to 1.00%. The new polymers are analyzed to monitor morphological changes, optical properties, mechanical properties and antioxidant and antimicrobial activities. Fourier transform infrared spectroscopy (FTIR) spectra of the new materials show the characteristic bands of the PVA alone and a modification of the band at around 1138 cm-1 and 1083 cm-1, showing an influence of the anthocyanins' addition on the sequence with crystalline and amorphous structures of the starting materials, as also shown by the results of the mechanical tests. These last showed an increase in thickening (from 29.92 μm to approx. 37 μm) and hydrophobicity with the concomitant increase in the added anthocyanins (change in wettability with water from 14° to 31°), decreasing the poor water/moisture resistance of PVA that decreases its strength and limits its application in food packaging, which makes the new materials ideal candidates for biodegradable packaging to extend the shelf-life of food. The functionalization also determines an increase in the opacity, from 2.46 to 3.42 T%/mm, the acquisition of antioxidant activity against 2,2-diphenyl-1-picrylhdrazyl and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals and, in the ferric reducing power assay, the antimicrobial (bactericidal) activity against different Staphylococcus aureus strains at the maximum tested concentration (1.00% of anthocyanins). On the whole, functionalization with anthocyanins results in the acquisition of new properties, making it suitable for food packaging purposes, as highlighted by a food fresh-keeping test.

Eco-friendly tea waste magnetite nanoparticles for enhanced adsorptive removal of norfloxacin and paroxetine from water

Traces of pharmaceuticals have been detected in water cycle raising concerns regarding the potential risks to human health and aquatic environment. Accordingly, removal of such compounds from water samples is a major concern. Herein, a facile and green NaOH modified tea waste magnetite nanoparticles have been fabricated for the adsorptive removal of a commonly used antibiotic (norfloxacin) and antidepressant (paroxetine) from water samples. The synthesized nanoparticles were characterized using TEM, FT-IR, DLS and VSM. Factors affecting the adsorption efficiency have been investigated with respect to pH (5, 7 and 9), adsorbent amount (0.125, 0.25 and 0.5 g), initial drug concentration (25, 50 and 100 µg/mL) and contact time (0.5, 1 and 2 h). The adsorption isotherms have been calculated. A percentage removal of 98 % and 99 % were obtained for simultaneous removal of 50 µg/mL norfloxacin and paroxetine, respectively in 2 h. Monitoring norfloxacin and paroxetine concentrations was performed through a validated HPLC-DAD method. The reusability of the nanoparticles has been studied for 3 adsorption–desorption cycles. No significant loss in adsorption efficiency was observed offering a sustainable water treatment. This study would offer a facile, green and economic protocol for the removal of complex organic compounds from water resources.

Mining for antifungal agents to inhibit biofilm formation of Candida albicans: A study on green synthesis, antibiofilm, cytotoxicity, and in silico ADME analysis of 2-amino-4H-pyran-3-carbonitrile derivatives

Candida albicans (C. albicans) biofilm infections are quite difficult to manage due to their resistance against conventional antifungal drugs. To address this issue, there is a desperate need for new therapeutic drugs. In the present study, a green and efficient protocol has been developed for the synthesis of 2-amino-4H-pyran-3-carbonitrile scaffolds 4a-i, 6a-j, and 8a-g by Knoevenagel-Michael-cyclocondensation reaction between aldehydes, malononitrile, and diverse enolizable C-H activated acidic compounds using guanidinium carbonate as a catalyst either under grinding conditions or by stirring at room temperature. This protocol is operationally simple, rapid, inexpensive, has easy workup and column-free purification. A further investigation of the synthesized compounds was conducted to examine their antifungal potential and their ability to inhibit the growth and development of biofilm-forming yeasts like fungus C. albicans. According to our findings, 4b, 4d, 4e, 6e, 6f, 6g, 6i, 8c, 8d, and 8g were found to be active and potential inhibitors for biofilm infection causing C. albicans. The inhibition of biofilm by active compounds were observed using field emission scanning electron microscopy (FESEM). Biofilm inhibiting compounds were also tested for in vitro toxicity by using 3T3-L1 cell line, and 4b, 6e, 6f, 6g, 6i, 8c, and 8d were found to be biocompatible. Furthermore, the in silico ADME descriptors revealed drug-like properties with no violation of Lipinski's rule of five. Hence, the result suggested that synthesized derivatives could serve as a useful aid in the development of novel antifungal compounds for the treatment of fungal infections and virulence in C. albicans.

Brønsted Acidic Ionic Liquid: An Efficient Organocatalyst for the Synthesis of Pyrrolo[1,2‐a]indoles under Neat Conditions

A new synthetic approach has emerged for constructing the 9H-pyrrolo[1,2-a]indole scaffolds by the reactions between indoles and chalcones under metal and solvent-free conditions at 80 °C. The reaction occurs smoothly in presence of Brønsted acidic ionic liquid named 1-butane sulfonic acid-3-methylimidazolium tosylate, [BSMIM]OTs (BAIL) as a catalyst, enabling the synthesis of the desired products with satisfactory yields. The developed protocol is applicable for the construction of biologically important pyrrolo[1,2-a]indole derivatives from easily accessible chalcones having various substituents. The process commenced with Michael addition to chalcones, followed by annulations induced by the elimination of a water molecule yielded the 9H-pyrrolo[1,2-a]indole scaffolds. Few control experiments were carried out for better understanding the reaction pathway. The feasibility of catalyst recycling was also demonstrated. This method produces only water as the byproduct and represents a green synthetic protocol. Clean reaction, easily accessible reactants, and metal and solvent-free and environmentally friendly reaction conditions are the notable advantages of this procedure.

Achieving Record C2H2 Packing Density for Highly Efficient C2H2/C2H4 Separation with a Metal–Organic Framework Prepared by a Scalable Synthesis in Water

AbstractAdsorptive C2H2/C2H4 separation using metal–organic frameworks (MOFs) has emerged as a promising technology for the removal of C2H2 (acetylene) impurity (1 %) from C2H4 (ethylene). The practical application of these materials involves the optimization of separation performance as well as development of scalable and green production protocols. Herein, we report the efficient C2H2/C2H4 separation in a MOF, Cu(OH)INA (INA: isonicotinate) which achieves a record C2H2 packing density of 351 mg cm−3 at 0.01 bar through high affinity towards C2H2. DFT (density functional theory) calculations reveal the synergistic binding mechanism through pore confinement and the oxygen sites in pore wall. The weakly basic nature of binding sites leads to a relatively low heat of adsorption (Qst) of approximately 36 kJ/mol, which is beneficial for material regeneration and thermal management. Furthermore, a scalable and environmentally friendly synthesis protocol with a high space‐time yield of 544 kg m−3 day−1 has been developed without using any modulating agents. This material also demonstrates enduring separation performance for multiple cycles, maintaining its efficacy after exposure to water or air for three months.

Palladium‐Catalyzed Denitrogenative Coupling of Aryldiazonium Salts with Terminal Alkynes for the Assembly of Internal Alkynes

AbstractAn N‐heterocyclic carbene palladium (NHC‐palladium)‐catalyzed denitrogenative coupling of aryldiazonium salts with terminal alkynes in ionic liquids has been accomplished. This catalytic strategy provides an effective and green synthetic protocol for the assembly of structurally diverse internal alkynes with excellent functional group compatibility and mild conditions. In the presence of 1 mol % of IMes‐Pd‐Im‐Cl2 as the catalyst, a wide range of terminal alkynes and aryldiazonium salts could be excellently tolerated. Basic ionic liquid plays a crucial role in this catalytic system, which not only acts as the green solvent, but also provides basic environment for the carbon‐carbon bond formation process. Notably, this catalytic system could be recycled up to six times and reused without significant loss of catalytic activity.