A one-pot procedure for amide bond formation has been developed in the presence of TBAI/TBHP. 1,4-Dioxane serves dual roles as both solvent and a traceless acyl-activating agent for the direct coupling of carboxylic acids with primary and secondary amines, affording the corresponding amides with good to excellent yields. Moreover, the versatility of this strategy is also highlighted by the synthesis of pharmaceutically valuable amide bond-containing molecules such as Moclobemide, Trimethobenzamide, Olaparib, Mitapivat.
The U.S. Environmental Protection Agency (EPA) has placed a ban on most uses of dichloromethane (CH2Cl2) due to its highly toxic and carcinogenic nature. Several deaths have been attributed to CH2Cl2 exposure. Unfortunately, CH2Cl2 has been one of the most commonly used solvents in synthetic chemistry. For example, the peracid epoxidation of alkenes is typically carried out in dichloromethane as the solvent. With the goal of finding safer alternatives to CH2Cl2, we chose the MCPBA epoxidation of alkenes as a test reaction and explored the utility of benzotrifluoride (BTF) and 2-methyltetrahydrofuran (2-MeTHF) as solvents. Herein, we report the use of BTF and 2-MeTHF as viable alternatives to CH2Cl2 for the MCPBA epoxidation of alkenes.
Organic electrosynthesis represents a green alternative to conventional redox chemistry by replacing stoichiometric reagents with electrons. Nevertheless, direct anodic oxidation often leads to over-oxidation and poor selectivity. Iodide has emerged as an attractive, low-cost, and electrochemically regenerable redox mediator enabling indirect electrosynthetic transformations under mild conditions. This review highlights iodide-mediated organic electrosynthesis from a green chemistry perspective, covering diverse transformations such as C–N, C–C, C–S, S–S, S–O, S-N, and P-N bond formation, C–H functionalization, cyclization, and oxidative coupling. Rather than focusing on detailed mechanisms, the discussion emphasizes mediator function, reaction scope, waste minimization, and sustainability-related advantages, including reduced oxidant use and improved selectivity. Current limitations and future opportunities for iodide-mediated electrosynthesis in sustainable organic synthesis are also outlined.
Mechanochemical methods provide a solvent-minimised, energy-efficient route for performing common transformations in carbohydrate chemistry. This paper reports optimised protocols for the mechanochemical protection of monosaccharides and disaccharides to deliver O-benzoyl-protected sugars. We compare yields, selectivity, and reaction times with classical solution-phase methods and provide mechanistic insight from control experiments and spectroscopic characterisation (NMR and IR). The mechanochemical approach exhibits comparable selectivity, shorter reaction times, and improved sustainability metrics, such as the E-factor and solvent use, while also providing a unique response to different sugars under the same reaction conditions. Importantly, direct benzoylation with p-nitrobenzoic acid and p-chlorobenzoic acid produced the desired benzoyl derivatives in high yields, indicating a cost-effective process.
Small chiral molecules are of great value not only because of their recurrent unique chemical reactivity and ready application in the pharmaceutical and food industries, but also because they constitute building blocks for the synthesis of more complex molecules with relevant biological activity. On the other hand, the development of chemical processes that are both highly efficient and environmentally friendly is one of the most rapidly growing areas of research in recent years, particularly when the goal pertains the preparation of relevant molecules and useful chemical materials. This mini review highlights illustrative examples of the application of mechanosynthesis and mechanoenzymology in the development of highly efficient chemical processes involving minimum use of solvents, affording “green” strategies for the stereoselective synthesis of valuable small chiral molecules.
Deep eutectic solvents (DESs) are a promising class of mixtures known for their significantly lower melting points compared to their individual constituents. They share similar physical properties with ionic liquids (ILs) but offer more advantageous characteristics such as low cost, easy preparation, and environmental friendliness. This review provides a brief account of various types of DESs and their potential applications in organic transformations and metal-extraction studies. In particular, natural deep eutectic solvents (NADESs) have demonstrated their importance in various fields of research, including biocatalysis, depollution, electrochemistry, and biomedical applications. However, it is imperative to explore the advantages of NADESs over conventional volatile organic solvents and ILs in terms of cost-effectiveness, green and sustainable nature, promising designability, biosafety profiles, and correlations between the compositions and combinations of constituents. Without a doubt, addressing these tasks will improve the understanding of this novel class of solvents at the molecular level and thereby enable new ways to utilize the special features of NADESs in future applications.
A non-catalytic method for the para-hydroxybenzylation of NH-azoles that differ significantly in nucleophilicity and basicity (imidazoles, benzimidazoles, 1,2,4-triazoles and others) with p-hydroxybenzyl alcohols in the absence of solvent has been developed. The synthesis uses available reagents and is characterized by high product yields, short reaction times, simplicity of isolation and purification, and high atom economy.
Green chemistry approaches are increasingly relevant for the sustainable development of functional nanomaterials with biomedical potential. In this work, nanodiamonds (NDs) were functionalized through an environmentally friendly ultrasonication-assisted method using (3-aminopropyl)triethoxysilane, di-tert-butyl peroxide, hydrogen peroxide, and ascorbic acid, avoiding harsh conditions and toxic reagents. Comprehensive physicochemical characterization confirmed successful surface modification for all functionalized nanodiamonds (FNDs).The biological performance of the resulting nanosystems was evaluated through antibacterial assays against Staphylococcus aureus and Escherichia coli, as well as antioxidant and cytoprotective tests. Amino- and peroxide-functionalized NDs exhibited selective antibacterial activity, with significant reductions in viable S. aureus counts in the concentration range between 100 and 500 μg/mL, whereas antibacterial effects against E. coli were limited and surface-chemistry dependent. In contrast, ascorbic acid–functionalized nanodiamonds (ND-AA) displayed pronounced antioxidant behavior, with a DPPH radical scavenging EC50 of 17 ± 3 μg/mL and a Trolox equivalent antioxidant capacity of 759 ± 45 μmol TE/g. Notably, ND-AA provided strong protection against oxidative hemolysis in human erythrocytes, achieving an IC50 of 8.2 ± 0.3 μg/mL, markedly outperforming free ascorbic acid.These results demonstrate that green ultrasonication-driven surface functionalization influences the bioactivity of nanodiamonds, allowing the selective design of antibacterial or antioxidant nanoplatforms. The proposed strategy highlights nanodiamonds as sustainable and versatile nanomaterials for advanced biomedical applications within a green chemistry framework.
Ionic liquids (ILs) have emerged as powerful enablers of sustainable chemistry, evolving beyond their initial role as low-volatility solvents to function as catalysts, mediators of reactivity, and recyclable platforms for diverse transformations. Their distinctive physicochemical properties, including negligible vapor pressure, tunable polarity, and high thermal stability, have positioned them as attractive alternatives in green synthetic methodologies when judiciously designed and applied. Among the many applications of ILs, the synthesis of oxygen-containing heterocycles represents a particularly dynamic and impactful area, given the central role of oxiranes and furans in pharmaceuticals, natural products, and biomass-derived value-added chemicals.This review highlights major advances reported over the past 25 years in ionic-liquid-mediated sustainable synthesis of mono-oxygen three- and five-membered oxygen heterocycles. The discussion is based on a curated selection of representative contributions that illustrate key methodological developments, mechanistic features, and context-dependent green chemistry benefits enabled by ionic liquids. Notably, ionic-liquid-mediated approaches to four-membered oxygen heterocycles remain largely unexplored, and only a single review (published in 2018) has addressed this field to date, underscoring the timeliness of the present work.By critically analyzing reaction design, mechanistic insights, sustainability considerations, and inherent limitations, this article highlights how ionic liquids can enable improved selectivity, reduced energy input, and efficient catalyst recycling under optimized conditions. The discussion further emphasizes emerging trends, including the use of functionalized and bio-derived ionic liquids, integration with renewable feedstocks, and hybrid systems that bridge homogeneous and heterogeneous catalysis. Collectively, this review demonstrates that ionic-liquid-mediated synthesis of small oxygen heterocycles extends beyond solvent replacement toward a broader paradigm of reaction engineering, offering valuable directions for future advances in green heterocyclic chemistry.
An efficient, scalable and sustainable approach for the microwave-assisted synthesis of β-keto esters is described. It is based on microwave activation of 2,2,6-trimethyl-4H-1,3-dioxin-4-one in the presence of an alcohol. This solvent- and catalyst-free methodology proved efficient with a range of alcohols regardless of their steric bulkiness and electronic nature. The method tolerates a range of substitution. It provides high yields and very low E-factors, acetone being the only byproduct. The products can generally be isolated by distillation or precipitation, overall offering a highly sustainable process.
Building on previous efforts in optimizing the synthesis of 1,2,3,4,5-pentathiepino[6,7-a]indolizines mediated by the molybdenum oxo bistetrasulfido complex, this study advances the respective preparation procedures by introducing an environmentally friendly approach with a concomitant focus on increasing yields and efficiency, and generally improved reaction conditions. Incorporating the sustainable solvent Cyrene™ into the established protocol enables the synthesis of various substituted 1,2,3,4,5-pentathiepino[6,7-a]indolizines in a more environmentally friendly manner, complemented by a new purification approach. Derivatives studied include substituents CF3, CN, CHO, COOMe, and a urea group at C-9. Realized modifications with a COOMe group at positions C-8, C-10, and C-11 are reported for the first time. Testing three different sets of conditions confirmed that the green Cyrene™ is a valid practical alternative to dimethylformamide (DMF). Although yields and reaction times did not improve in each and every case, the research demonstrates a method utilizing a non-toxic, biodegradable solvent to comprise a significant advancement over traditional, more toxic, and harsh methods for this compound class. Sublimation as a new purification technique was also explored in order to minimize the generation of organic solvent waste. Notably, the CN-substituted compound showed unusual behaviour during synthesis, with no product formation under N2 conditions, and unexpected tetrasulfide side products could be identified for two COOMe derivatives. To understand the observed differences in reactivity and the chemical/molecular and electronic structures of these compounds, comprehensive analytical characterization was performed on all derivatives supported by computational analysis.
This study aimed to develop an efficient photocatalyst for the degradation of Brilliant Blue G (BBG) dye in aqueous solutions under visible light and ozonation. The research focused on synthesising and characterising a novel Bi2O3/MWCNT@TiO2 nanocomposite (BMT) to enhance photocatalytic performance through synergistic effects. The Bi2O3/MWCNT@TiO2 nanocomposite was prepared using a wet impregnation method. Techniques such as PXRD, UV–visible DRS, BET surface area analysis, SEM-EDX, and TEM were employed to evaluate structural and morphological properties. Variants, BMT-1 to BMT-5, were synthesised with varying compositions and extensively characterised. The results revealed that BMT-1 and BMT-5 exhibited particle sizes in the range of 20–45 nm and band gaps of 2.76 eV and 3.0 eV, respectively, indicating their suitability for visible-light-driven photocatalysis. The nanocomposites demonstrated exceptional efficiency in degrading BBG dye under solar irradiation and ozonation. At an optimal catalyst dose of 0.025 g/L and an initial dye concentration of 20 ppm, a maximum degradation efficiency of 98.3 % was achieved. The influence of pH was investigated at acidic (pH 3), natural, and alkaline (pH 11) conditions. BMT-5 exhibited superior performance at the dye's natural pH, while BMT-1 showed high degradation of 97 % and 93 % at pH 3 and 11, respectively. Additionally, the catalysts displayed excellent reusability, confirming their stability and potential application for practical wastewater treatment applications. This work highlights the usefulness of Bi2O3/MWCNT@TiO2 as a robust photocatalyst for pollutant degradation under environmentally relevant conditions.
As the demand for chemists to adhere to green chemistry principles increases, so does the demand for green solvents. Unfortunately, many green solvents, such as 2,2,5,5-tetramethyltetrahydrofuran (TMTHF), are costly and difficult to source. Traditional synthesis of TMTHF from 2,5-dimethyl-2,5-hexanediol has been reported to be catalysed by acids such as phosphoric and sulfuric acid, or, more recently, by H-beta zeolite. Although H-beta zeolite catalysts are high-yielding and selective, the energy required for their regeneration is high, and their production has questionable environmental impacts. A new approach was developed using flow technologies and naturally occurring acids as catalysts for TMTHF synthesis. Flow technologies are scalable, safe, efficient, and reproducible for daily chemical reactions, aligning with principles of green chemistry. This study observed several key improvements, including i) the use of a natural acid as a catalyst, ii) the use of water as a solvent, and iii) a continuous process for multigram-scale synthesis of TMTHF using citric acid monohydrate, with a yield of 72 %, resulting in a throughput of 8.24 g h−1 (9.43 kg L −1 h−1 space-time yield).
Transforming lignin into valuable aromatic compounds is a critical objective for sustainable biorefining. While oxidative depolymerization has been proven effective in breaks down lignin’s macromolecule, its practical application has been limited by low selectivity. This review presents a paradigm shift in the field, moving from broad, non-selective oxidative degradation methods to highly targeted catalytic processes driven by controlled reactive oxygen species (ROS). It offers a comprehensive analysis of how various catalytic systems—utilizing O2, H2O2, metals oxides, electricity, light, and organic oxidants—generate distinct ROS profiles, ranging from non-specific hydroxyl radicals to more selective superoxide anions or high-valent metal-oxo complexes. These ROS serve as "molecular scissors", directly influencing the efficiency of C–O and C–C bond cleavage, thereby determining the yields of key products such as aldehydes, ketones, and acids. This review also explores emerging strategies, including single-atom catalysis and external field activation, which provide unparalleled precision in managing these reactive intermediates. Finally, it addresses ongoing challenges related to catalyst stability and the heterogeneity of lignin, while outlining promising future research directions focused on tandem processes and real-time mechanistic studies, to further unlock lignin's potential as a renewable source of aromatic feedstocks.
The amine-catalyzed aldol reaction has become a stable of organic synthesis with numerous applications affording predominantly the anti aldol product. Using our synthesized and characterized bile acid-amino acid conjugates with l-proline and l-phenylalanine, and bile acids amino derivatives we successfully performed regioselective aldol reactions in aqueous media controllably giving either the anti or syn diastereomer. These novel derivatives exhibited high catalytic activity, with the l-proline-based organocatalyst showing the highest efficiency, achieving yields up to 99 %, high diastereoselectivity for the anti product and moderate enantioselectivity. The l-phenylalanine-based one demonstrated good catalytic performance, achieving yields up to 99 % and good diastereoselectivity for the syn product. The environmental sustainability of these catalytic systems was further enhanced in the use of bio-based surfactants-amino acids conjugates utilizing water as the reaction medium, without the addition of any cosolvent, while aligning with the modern ethics of environmentally friendly practices. These findings reveal the potential application of natural bile acids scaffolds as versatile and eco-friendly conjugates to afford highly efficiency in sustainable organocatalysis for successfully achieving organic transformations in aqueous environments.
Annulation of methyl C–H bonds in acetophenone derivatives with 2-phenylglycines to furnish 2,5-diphenyloxazoles under the assistance of heterogeneous catalyst is firstly reported. Successes are attributed to the use of commercially available copper iron oxide, in combination with molecular iodine, p-toluenesulfonic acid, and DMSO. The efficiency of our method is somewhat proven as 19 examples were isolated with yields varied from 32 % to 84 %. The copper iron oxide could be recovered and reused up to 4 times with nearly identical catalytic activity.
Green methods for synthesizing pyridopyrazinones were developed due to their usefulness as scaffolds in the design of therapeutic compounds. Reaction conditions using aqueous ethyl lactate solutions were optimized to maximize yields through direct product precipitation. Two key scaffolds, 3-methylpyrido[2,3-b]pyrazin-2(1H)-one and 2-methylpyrido[3,4-b]pyrazin-3(4H)-one, were obtained in yields of 88 % and 85 %, respectively. The highest yields were achieved using 92:8 and 99:1 ethyl lactate:water mixtures, with the latter including 1.5 mol% lactic acid at 35 °C. These results are comparable to traditional syntheses using anhydrous chloroform but offer a more sustainable alternative by avoiding hazardous solvents.
The destruction of the ecosystem caused by chemicals such as pesticides, fertilizers, plastics, and greenhouse gases has provoked the conscience of the public and regulators to control the use of chemicals. There is a growing concern and awareness about preserving the environment against the danger of toxic substances. Sustainable industrial development as a means of cutting pollution from industry and developing renewable raw materials for industry has been a challenge in the twenty-first century. This review outlines the basics and ideas of green chemistry with examples and emphasis on the synthesis of bioactive molecules—based quinazoline, quinoline, quinoxaline, benzimidazole and imidazole from 2012 to 2025 to illustrate different fronts for developmental improvement in achieving sustainable procedures.
Wastewater treatment is an environmental imperative due to increasing water stress and ecological crises particularly in view of the inherent limitations of conventional treatment methods, which frequently demonstrate suboptimal efficiency and tend to produce undesirable secondary by-products. In this context, advanced oxidation processes (AOPs), especially heterogeneous photocatalysis, have demonstrated significant potential as ecologically and economically viable solutions for the complete degradation of pollutants into CO2 and H2O under ambient conditions. Titanium dioxide (TiO2) is the most widely used photocatalyst owing to its non-toxicity, photochemical stability, and high reactivity. However, its practical application is hindered by several limitations, including activation restricted to UV light (due to a wide bandgap), rapid recombination of photogenerated electron–hole pairs, and relatively low surface area. To overcome these challenges, this review discusses recent strategies for modifying the properties and structure of TiO2 to enhance its photocatalytic performance under visible light. These strategies include metal or non-metal doping, the formation of heterostructures, and dye sensitization, all aimed at extending light absorption into the visible range and improving charge separation and transport. Furthermore, the integration of TiO2 with bismuth-based photocatalysts, such as BiVO4, Bi2WO6, and Bi2MoO6, is explored. These materials exhibit efficient visible-light absorption and favorable electronic properties, significantly boosting the photocatalytic activity of TiO2. By implementing these modifications, TiO2-based photocatalysts are expected to play a key role in environmental remediation and contribute to the development of sustainable water treatment technologies.
Modeling of Michael addition of pyrazole to cinnamaldehyde in the presence of six thiourea catalysts has been done at the DFT (B3LYP/6-31+G(d,p)) level. Four catalysts incorporating 2-pyridyl moiety are found to exhibit bifunctional dual activation by encapsulating pyrazole molecule in the cavity of cinnamaldehyde-catalyst complex thereby mimicking biosystem to bring the two reactants closer and also narrowing down the HOMO-LUMO gap. Guided by the theoretical results, four new N-bis(3,5-trifluoromethyl)phenyl-N′-2-pyridylthiourea catalysts were synthesized and well characterized on the basis of IR, 1H and 13C NMR and HRMS studies. X-ray crystal structure of one catalyst could also be done. On determining comparative catalytic efficacies of these catalysts experimentally for the model reaction of pyrazole with cinnamaldehyde, the catalyst N-bis(3,5-trifluoromethyl)phenyl-N′-2-(5-chloropyridyl)thiourea was found to be most effective, which is in accordance with the theoretical modeling results.
