Current Organic Synthesis - Volume 20, Issue 7, 2023

Background: A series of new eight 2-(1-aryl-3-methyl-1H-pyrazol-4-yl)-1,4,5,6-tetrahydropyrimidines 1(a-h) were synthesized by microwave irradiation technique. In vitro phenotypic screening was performed to evaluate the effect of these compounds on intracellular amastigotes forms of Trypanosoma cruzi, the etiological agent of Chagas disease. Methods: Compounds 1(a-h) were synthesized from pyrazole-carbonitriles 2(a-h) employing microwave irradiation (50W) for 10-20 minutes. Physicochemical properties were calculated using OSIRIS DataWarrior. The toxic effect on mammalian cells (Vero Cells) and the trypanocidal activity against Trypanosoma cruzi (Dm28c-Luc) were also evaluated. Results: Compounds 1(a-h) were obtained in 24-94% yields. They were completely characterized by Fourier Transform Infrared (FT-IR), Nuclear Magnetic Resonance (NMR) and High-Resolution Mass Spectrometry (HRMS) analyses. The derivatives showed low trypanocidal activity, with IC50 ranging from 47.16 to > 100 μM, with lower activity than benznidazole (1.93 μM) used as reference drug. Conclusion: The attractive features of this synthetic methodology are mild conditions, short reaction time, and low power. All derivatives showed low toxicity in mammalian cells, good oral bioavailability, and did not violate Lipinski´s rule of 5.

Background: Phenol and its derivatives are important intermediates in the chemical industry, especially the pharmaceutical and electronic industries. The synthesis of phenols has attracted the attention of scientists due to their importance. Dehydrogenation of cyclohexanones is one of the promising aromatization strategies for phenols manufacture because the raw materials are low cost and stable. In recent years, some efficient and green methods with the use of H2, O2 and air, alkene, H2 and O2-free are described. Objective: This mini-review will summarize some recent developments relating to the dehydrogenation of cyclohexanones to phenols, along with their interesting mechanism aspects. The challenges and future trends of the transformation will be prospected. Conclusion: The synthesis of phenols from the dehydrogenation of cyclohexanones has recently attracted much attention. Some synthetic methods have been established, and interesting mechanisms have been proposed in some cases. Lots of catalysts were developed for the transformation to afford the corresponding product. Although the present methods still have drawbacks and limitations, it is supposed that many novel methods would probably be developed in the near future.

Pyrimidine and Triazine are rewarding pharmacophores as seen from their presence in different naturally and synthetically occurring drug molecules. Hybridization is a functional concept used in drug design. This updated review encompasses various synthetic procedures that have been used to prepare molecular hybrids of Pyrimidine and Triazine, detailed structureactivity relationship, and molecular docking studies with patents granted. The most potent and promising hybrid compounds have also been identified. The study has revealed the synthetic feasibility of Pyrimidine-Triazine hybrids along with a plethora of potent biological activities such as anticonvulsant, antiviral, anti-inflammatory, analgesics, etc. This paper highlights the importance of coupling Pyrimidine and Triazine to provide better insight for medicinal chemists to further explore the hybrid for a significant therapeutic effect.

Due to their diverse applications in industrial and synthetic organic chemistry, quinoline and 1,3,4-oxadiazole have become important heterocyclic compounds. Quinoline and 1,3,4- oxadiazole compounds have been developed for various medical conditions such as anti-cancer, anti-bacterial, anti-fungal, antimalarial, antioxidants, anti-HIV, anticonvulsant, antiviral, etc. The current review includes synthetic protocols for biologically active 1,3,4-oxadiazole incorporating quinoline hybrids with their structure-activity relationship to explore work (Mainly from 2010 to 2021) based on 1,3,4-oxadiazole-quinoline hybrids to the medicinal chemist for further research in the development of the molecule.

Introduction: Nowadays, the catalysts' usage in chemical reactions is unavoidable, and this has led scientists to look for producing and using catalysts which not only cause pollution and toxicity in the reactions and products, but also generate economical benefits. Aims: Our goal in this paper is to produce a fully biocompatible, non-toxic and inexpensive carbocatalyst with a graphene oxide structure for use in multi-component reactions as a heterogeneous catalyst. Methods: The research has been carried out to simplify the method of preparing carbocatalysts. In this article, we heated citric acid and thiourea in the simple bottom-up method in which nitrogen and sulfur were atomically inserted into a carbon-carbon bond of graphene oxide. Results: The results have been obtained by comparing graphene oxide quantum dots (GOQDs) and functional graphene oxide quantum dots (GOQDs) and functional nitrogen and sulfur-doped graphene oxide quantum dots (NS-doped-GOQDS) using the produced carbocatalyst in the synthesis of spiro indoline pyrano pyrazoles and highly substituted pyridine derivatives with chemical and pharmacological properties. Conclusion: A simple and affordable bottom-up method has been developed to synthesize fluorescent NS-doped-GOQDS by the condensation of CA in the presence of thiourea with water elimination at 185 132;ƒ. After the production of NS-doped-GOQDS, the carbocatalyst is used in the synthesis of spiro[indoline-3,4'-pyrano [2, 3-c]pyrazole] derivatives in four-component reactions and pyridine derivatives in five-component reactions.

Background: New cyclohexenone derivatives candidates were designed to discover their antioxidant and antibacterial activity potentials, respectively. Methods: Aldehydes with the diverse functional group were prepared from 4-hydroxy benzaldehyde and benzyl bromide and converted to chalcones by reaction with 4-substituted benzophenones and 2-acetyl naphthalene. When chalcone derivatives were subjected to ethyl acetoacetate, it produced new cyclohexenone derivatives through NaOH- catalyzed addition-ring closure reaction. The new compound structures were strengthened by their spectral information. The new compounds are examined for in vitro antifungal and antibacterial actions through broth microdilution technique, and they exhibited potential responses against various bacteria and fungi. Results: As a result, composites with (-F) group as a substituent on para position were established to be the forceful derivatives against S. aureus, E. coli organism, and C Albicans since this compound could inhibit the microbial and Fungai growth at lower concentrations compared to the standards (Ciprofloxacin HCl, and Fluconazole). Conclusion: DPPH radical scavenging experiments were used to evaluate proton donating antioxidant effects; it was exposed that compound 7c has the most significant antioxidant activity, while less than the standard ascorbic acid. Finally, HOMO-LUMO was calculated, which represents the quantum mechanical calculations of energies and conducted by the theory of density functional (DFT) method based on the level of (B3LYP) with 6-31G (d, p) basis set.