Letters in Organic Chemistry - Volume 22, Issue 11, 2025

Herein, we disclose an eco-friendly route for the synthesis of 2,4,5-triaryl-1H-imidazole derivatives. One-pot, three-component synthesis involving benzil, substituted aromatic aldehydes, and ammonium acetate in the presence of a catalytic amount of trihexyltetradecyl-phosphonium bis(2,4,4-trimethylpentyl)phosphinate (PBIL) ionic liquid in ethanol at room temperature yields corresponding 2,4,5-triaryl-1H-imidazole derivatives in appreciable yield. The use of ionic liquid as a green catalyst with ethanol, which is considered to be an environmentally benign solvent, simple workup procedure, and appreciable yield of the product are some of the notable advantages of this method.

The current work describes a unique iodine-mediated intra-molecular rearrangement of amide to nitrile and thiourea to urea, which took place simultaneously in thiophenes. The thiophenes having amide and amine groups at the adjacent positions were prepared via the Gewald reaction and subsequently treated with isothiocyanates in the presence of molecular iodine to get 1-(3-cyanothiophen-2-yl)-3-phenylureas in good yields. The synthesized compounds are of particular interest both chemically and biologically, as they contain thiophene, urea, and nitrile moieties in a single molecule. Many thiophene derivatives have been reported to exhibit antioxidant properties. Hence, the synthesized molecules were screened for their antioxidant activity by means of scavenger activity towards 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the Ferric Ion Reducing Power (FRAP) assay. Some compounds exhibited promising antioxidant properties.

Steroidal saponins are natural compounds known to have anticancer activity by inducing apoptosis through inhibition of Bcl-2. This study was carried out on the potency, mechanism, and binding affinity of steroidal saponins present from Hoya verticillata var. verticillata as Bcl-2 inhibitor of colorectal cancer in silico using molecular docking and molecular dynamics simulation. All steroidal saponins exhibited hydrogen bonds in molecular docking, Van der Waals, and hydrophobic interactions. The binding potentials of steroidal saponins collected in previous studies and a reference compound, navitoclax, as target protein 6GL8 of BCL-2 inhibitor of colorectal cancer, were examined using molecular docking. The results showed the binding stabilities as -8.28, -8.87, -9.29, -11.09, -11.16, and -8.34 kcal/mol, respectively. Given the limited in-silico studies on pregnane saponins, we considered the extensive interest in these compounds. So, molecular dynamics studies were carried out to better comprehend the dynamics of ligands within the binding pocket of the target protein. Molecular dynamics simulation revealed that the binding of parasiticoside B to the 6GL8 receptor was stable and strong, based on their RMSD, RMSF, and the number of hydrogen bonds throughout the simulation. From the molecular interaction analysis derived from molecular dynamic trajectories of each ligand-bound complex, these interacting amino acids might be determined to play a crucial role in binding with the ligands of the 6GL8 active site. Parasiticoside B could be a good candidate for new inhibitors of anti-apoptotic BCL-2 proteins in colorectal cancer.

A novel and efficient method for synthesizing various quinoxaline derivatives has been developed, utilizing rainwater as both a solvent and a catalyst. This approach represents a significant advancement in green chemistry, as it combines simplicity, rapidity, and convenience while avoiding the need for toxic or expensive reagents. The synthesis involves the condensation reaction of aromatic 1,2-diamines with aromatic 1,2-dicarbonyl compounds. Traditionally, these reactions require specialized solvents and catalysts, but in this method, rainwater serves a dual function, streamlining the process and minimizing environmental impact. The use of rainwater not only simplifies the reaction setup but also provides an eco-friendly alternative to conventional organic solvents. The condensation leads to the formation of quinoxaline derivatives, a class of compounds known for their diverse biological and pharmacological activities. The reaction proceeds smoothly at ambient temperature, significantly reducing the energy requirements typically associated with chemical syntheses. This innovative synthesis method demonstrates the potential of using natural resources like rainwater in chemical reactions, contributing to sustainable practices in the field of organic synthesis. The versatility of the approach allows for the preparation of a variety of quinoxalines, offering promising applications in medicinal chemistry and material science. The rapid and straightforward process opens new avenues for the synthesis of quinoxalines, showcasing the potential of rainwater as a green solvent and catalyst in synthetic chemistry.

Novel simple approach was elaborated for the preparation of fentanyl and sufentanil starting from commercially available, cheap 1-methyl-4-piperidone. Compared to existing syntheses new route is shorter, easily scalable, and does not require the use of expensive palladium catalysts, high-pressure equipment, and chromatographic separations. Moreover, it allows for to avoidance of working with the unstable norsufentanil, which is prone to a facile acyl migration to the nitrogen atom of the piperidine core even at ambient temperature, resulting in contamination of the target product.

3, 3-di(indolyl)indolin-2-one derivatives have attracted the attention of researchers due to their various biological and medicinal applications. Due to the significant importance of indole compounds, various methods with different conditions and catalysts have been used for their synthesis. However, some of these reactions have disadvantages, such as low efficiency, long reaction time, use of toxic solvents, etc. In the study, iron nanocatalysts have been used as a suitable catalyst to prepare 3, 3-di(indolyl)indolin-2-one derivatives. This method has many advantages compared to other methods and it completes the reaction in a shorter time and with a higher yield, as described in this article.

A new series of low molar mass mesogens having double lateral substituents were prepared and characterized with the objective to explore the effect of structure modification on the mesomorphic behavior. The molecular structure has three aromatic rings at the centre core system, which is connected by an imine linking group, two flexible alkyloxy chains at both sides of molecules and two lateral methyl groups attached to the core system. This low molar mass mesogen is known as bis(4-alkyloxybenzylidene)-2,5-dimethyl-1,4-phenylenediamine with different numbers of carbon (n) at the alkyloxy chain. Molecular structures were confirmed via infrared and nuclear magnetic resonance spectroscopic and mass spectrometric methods. Phase transition studies were conducted using a differential scanning calorimeter. Whereas, mesophase characterization was determined by polarizing optical microscopy and the temperature was varied with a temperature controller. The current core system of benzylidene-1,4-phenylenediamine showed good potential of exhibiting liquid crystal as all compounds were found to exhibit a nematic phase. Double lateral methyl atoms at the central mesogenic core had broadened the molecular width. This has caused a reduction in the overall lateral intermolecular attraction, and therefore, it exhibited a nematic phase. As the number of carbons at the alkyloxy chain increased, the clearing temperatures were observed to show a descending trend. A comparison of thermal properties was made between the current compounds with analogous compounds that do not possess any lateral substituent or have a single lateral substituent attached to the mesogenic core.

Understanding the rotational barriers (RBs) and bond dissociation enthalpies (BDEt) of substituted aromatic compounds is crucial for predicting their chemical reactivity and stability. The RBs for 26 varying para-substituted anilines, benzaldehydes, and toluenes around the respective phenyl-NH2, -CHO, and -CH3 bonds, as well as around the corresponding radical phenyl-NH, -CO, and -CH2 bonds, were computed, based on the Density Functional Theory (DFT). The BDEt of the aminic N-H, CO-H, and methyl C-H bonds in the respective neutral molecules was also computed. The RBs and various geometric, molecular, and atomic properties were used to explain how the substituents influence the BDEt. The trends were rationalized by considering the relative stabilization/destabilization of the parent neutral molecules versus the corresponding radicals. This study is the first in which trends in the RBs and BDEts are rationalized by considering the effect of substituent, providing valuable information for understanding the fundamental behavior of substituted aromatics.