Letters in Organic Chemistry - Volume 19, Issue 7, 2022

An efficient and green protocol has been introduced for the synthesis of benzimidazole derivatives using a pyruvic acid catalyst in the presence of water. Pyruvic acid catalyses the reaction of aromatic aldehydes with o-phenylenediamine efficiently, and products were obtained in good to excellent yields under sonication (50 °C) or under conventional heating (50 °C). The advantages of this synthetic methodology are the use of eco-friendly, commercially cheap, biodegradable catalyst, metal-free and Lewis acid-free mild reaction conditions with excellent yields, short reaction times, and compatible with a wide range of electronically diverse substrates. Pyruvic acid in water as a catalyst under ultrasound irradiation can be a better alternative to synthesize benzimidazole derivatives than some of the traditional methods.

Construction of the C-C bond has been a challenge for organic chemists because of the reactivity of carbon atoms. The development of nucleophilic carbon was started with the Grignard reagent, enolate, and then ylide, however, the aromatic carbon activation was challenging till the era of organometallic chemistry. The organometallic chemistry was recognized when the Nobel Prize 2010 was given for the C-C bond forming organmetallic reaction; however, the pre functionalization of the C-H bond was an additional step with halogenated reagent, which was the limitation of this reaction. Later, the C-H activation with organometals like Pd, Ru, Cu, Rh, and other transition metal came into existence, where the directing group and metals were found to be sufficient to form the nonreactive C-C bond. In spite of several organometals, Ru acquired a special place due to the reactivity, cost and, stability. Various C-H activation reaction protocols were reported with their high regioselectivity as well as high atom economy. The C-H activation protocol involves the next level of development like SP3, SP2 ortho, meta, and para C-H activation. Here, our aim is to summarize the information regarding Ru and their ortho -regioselective reactions with the help of directing groups. The reader will benefit from the concept and the mechanism of C-H activation with the relevant examples, which have been summarized herein with the various Ru based regioselective reactions through weak and strong coordination of metal and substrate.

This study describes the synthesis of the pyrido[1,2-a]azepine alkaloids. The bicyclic compound 1 containing the A-B core ring structure was synthesized in 17 steps in 1.7% overall yield starting from 4-pentyn-1-ol. The key steps involve an oxidation of 1,4 diol to lactone and an ene-yne ring closing metathesis reaction.

A highly efficient heterogeneous nanocatalyst based on modified poly (styrene-altmaleic anhydride) (MPSAMA) in three steps was fabricated. Then, the MPSAMA surface was modified using chlorosulfonic acid (CAS) to achieve a sulfonated MPSAMA (SMPSAMA) with high acidity and efficiency. FT-IR spectroscopy, CHNS analysis, FESEM, and TGA were employed to characterize the prepared nanocatalyst. The catalytic activity of the SMPSAMA was examined for the formation of the polyhydroquinoline derivatives through Hantzsch condensation and the synthesis of 2-amino-4H-chromene derivatives. This new heterogeneous nanocatalyst has been efficiently used for the synthesis of bifunctional bis polyhydroquinoline, and new alkylene bridging bis 2-amino-5-oxo-5,6,7,8-tetrahydro-4H-benzo[b]pyran derivatives.

In this study, two novel hybrid series of artemisinin and quinazolinones were synthesized and evaluated in vitro cytotoxicity against two human cancer cell lines, including SKLu-1 (lung cancer), MCF- 7 (breast cancer). The bio-assay results indicated that most of the target compounds exhibited cytotoxic activities against both human cancer cell lines tested and seemed to be more cytotoxic toward the breast (MCF-7) cancer cells than lung (SKLu-1) cancer cells. Among the synthesized artemisinin hybrids, the compound 13d containing a quinazolinone conjugated system exhibited the most potent cytotoxicity against the SKLu-1 and MCF-7 cell lines with IC50 values of 1.62 and 0.77 μM, respectively. This study aims at developing novel hybrids of artemisinin and quinazolinones as anti-cancer agents. A series of novel hybrids were designed, synthesized, and evaluated for cytotoxicity against two human cancer cell lines, including SKLu- 1 and MCF-7, using the SRB method. All thirteen hybrids of artemisinin with quinazolinone exhibited cytotoxic activity against two tested cancer cell lines, in which the compound 13d exhibited the most potent cytotoxicity against the SKLu-1 and MCF-7 cell lines with IC50 values of 1.62 and 0.77 μM, respectively. The research results suggest that some compounds could be considered as leads for future design of hybrids and have the potential for further studies in the field of anti-cancer agent development.

Bifunctional ionic liquid [BIL] was found to be a highly effective catalyst for ether synthesis without any inorganic base or solvent. Using this protocol, different aryl substitutions were reacted with different phenols in good to excellent yields. The BIL is reusable without any loss in catalytic activity for nine consecutive cycles. The Williamson reaction is a convenient renovation in fine chemical synthesis since the ethers are important in both bulk and fine industrial chemicals preparation and academic applications. The aim of this study is to highlight the use of BIL to synthesize mixed ethers using substituted phenols and to study the reusability in the next cycle. The mixture of the phenol (1mmol), alcohol (1.2 mmol), and BIL ionic liquid (0.3 mol%) was added to a round-bottomed flask (100 mL) with continuous stirring for 1 hour. The products obtained were phenol and substituted phenols containing withdrawing substituents in respectable yields. However, the reactions involving substituted phenols containing electron-donating groups often afford the corresponding products in low yields. BIL is found to be an effective catalyst in the etherification of various unsymmetrical ethers under mild conditions. Bifunctional ionic liquid as a solvent and catalyst will show real rewards by providing a ‘green’ method with the safer procedure, less reaction time periods, mild conditions, easy separation, and ionic liquid recycle.

NiO nanoparticles are utilized to effectively strengthen annulated pyrano [2,3-d] pyrimidine synthesis through primary Knoevenagel, following Micheal and ultimate heterocyclization reactions of aldehyde, malononitrile, and barbituric acid. The characteristics of NiO nanoparticles are identified using advanced techniques, such as IR, UV, EDX, XRD, SEM, and TEM. The nano-NiO particles are mostly below < 100 nm in size with uniform spherical shapes. The adopted approach is advantages owing to its simple processing, relatively short reaction time, often good to high average yields, convenient workability, and environmental friendliness.

The adsorption of the Lenalidomide (LNA) drug on the surface of the B12N12 nanocluster has been studied using DFT and TD-DFT calculations. The quantum calculations have been performed at the B3LYP/6-311+G** level of theory in the solvent water. The change of DM also displays a charge transfer between LNA and nanocluster. The adsorption of the LNA drug from the O1 atom on the B12N12 nanocluster leads to higher electrical conductivity due to the low Eg rather than the other active sites. According to QTAIM analysis, -G(r)/V(r) values for B-O and B-N bonds are between 0.5 and 1, confirming the partially covalent character. The values of LOL and ELF are low in the region between the nitrogen and oxygen atoms of LAN and B12N12, which show that the interactions have mainly non-covalent character. The calculated data revealed that the B12N12 nanocluster can be an appropriate biomedical carrier for the delivery of LNA drugs.