A microwave assisted method for synthesis of 2-substituted benzimidazoles has been developed. The combination of molar ratio N-phenyl-o-phenylenediamine:benzaldehyde (1:1) using microwave irradiation and only 1% mol of Er(OTf)3 provide an efficient, environmental and mild access to a diversity of benzimidazoles under solvent-free conditions.

The use of alternative synthetic methods, in the face of traditional processes that do not conform to the principles of Green Chemistry, represent a problem in the pharmaceutical industry. The procedures for the synthesis of benzimidazole derivatives have become a focus in synthetic organic chemistry, as they are building blocks of strong interest for the synthesis of compounds with pharmacological activity. Various benzimidazole derivatives have found very strong application in medicine and their synthesis is reported in the literature. A simple and environmental Montmorillonite K10 (MK10) catalyzed method for the synthesis of benzimidazole derivatives has been developed. The use of MK10 as heterogeneous catalysis provides various advantages in terms of yields, in the work up procedure of the reaction, selectivity and the possible recycle of catalyst without waste formation. The reactions were carried out in solvent free condition and in short reaction time using an inexpensive and environmentally friendly heterogeneous catalysis and it has been shown that the reaction process is applicable in the industrial field.

Newly designed pentacyclic benzimidazole derivatives, featuring amino or amido side chains, were synthesized to assess their in vitro antiproliferative activity. Additionally, we conducted investigations into their direct interaction with nucleic acids, aiming to uncover potential mechanisms of biological action. These compounds were synthesized using conventional organic synthesis methodologies, alongside photochemical and microwave-assisted reactions. Upon synthesis, the newly derived compounds underwent in vitro testing for their antiproliferative effects on various human cancer cell lines. Notably, derivatives 6 and 9 exhibited significant antiproliferative activity within the submicromolar concentration range. Our biological assessment highlighted that the biological activity was strongly influenced by both the position of the N atom on the quinoline moiety and the position and nature of the side chain on the pentacyclic skeleton. Findings from fluorescence, circular dichroism spectroscopy, and thermal melting assays indicated a mixed binding mode—comprising intercalation and the binding of aggregated compounds along the polynucleotide backbone—of these pentacyclic benzimidazoles with DNA and RNA.

Heterocycles are unique precursors for the synthesis of various pharmaceuticals and agrochemicals particularly those possessing N- or O- moieties. The development of methods to prepare heterocycles is of great importance in synthesis of organic compounds, especially the heterocycles which can be found in natural products. The synthesis of nitrogen and oxygen containing heterocycles viz. coumarins, dihydropyrimidinones, imidazoles, isoxazoles and benzimidazoles represented an attractive and demanding work for chemists as these nucleus has found extensive applications in several fields such as material science, analytical chemistry and most importantly in medicinal chemistry. Organic synthesis has been attracted towards the development of new environmental friendly procedures to achieve the goals of green chemistry. The fundamental aspects of green chemistry are use of biocatalysts and environmental benign solvents under mild conditions. The present review article summarized the green synthetic methods and biological activities of nitrogen and oxygen containing heterocycles.

The exploitation and use of alternative synthetic methods, in the face of classical procedures that do not conform to the ethics of Green Chemistry, represent an ever present problem in pharmaceutical industry. The procedures for the synthesis of benzimidazoles have become a focus in synthetic organic chemistry, as they are building blocks of strong interest for the development of compounds with pharmacological activity. Various benzimidazole derivatives exhibit important activities such as antimicrobial, antiviral, anti-inflammatory and analgesic and some of the already synthesized compounds have found very strong application in medicine praxis. Here we report a selective and sustainable method for the synthesis of 1,2-disubstituted or 2-substituted benzimidazoles, starting from o-phenylenediamine in the presence of different aldehydes. The use of deep eutectic solvent (DES) both as reaction medium and reagent without any external solvent provides advantages in terms of yields as well as in the work up procedure of the reaction.