Current Organic Synthesis - Volume 20, Issue 2, 2023

Benzimidazole (BI) and its derivatives are interesting molecules in medicinal chemistry because several of these compounds have a diversity of biological activities and some of them are even used in clinical applications. In view of the importance of these compounds, synthetic chemists are still interested in finding new procedures for the synthesis of these classes of compounds. Astemizole (antihistaminic), Omeprazole (antiulcerative), and Rabendazole (fungicide) are important examples of compounds used in medicinal chemistry containing BI nuclei. It is interesting to observe that several of these compounds contain 2-aminobenzimidazole (2ABI) as the base nucleus. The structures of 2ABI derivatives are interesting because they have a planar delocalized structure with a cyclic guanidine group, which have three nitrogen atoms with free lone pairs and labile hydrogen atoms. The 10-π electron system of the aromatic BI ring conjugated with the nitrogen lone pair of the hexocyclic amino group, making these heterocycles to have an amphoteric character. Synthetic chemists have used 2ABI as a building block to produce BI derivatives as medicinally important molecules. In view of the importance of the BIs, and because no review was found in the literature about this topic, we reviewed and summarized the procedures related to the recent methodologies used in the N-substitution reactions of 2ABIs by using aliphatic and aromatic halogenides, dihalogenides, acid chlorides, alkylsulfonic chlorides, carboxylic acids, esters, ethyl chloroformates, anhydrides, SMe-isothioureas, alcohols, alkyl cyanates, thiocyanates, carbon disulfide and aldehydes or ketones to form Schiff bases. The use of diazotized 2ABI as intermediate to obtain 2-diazoBIs was included to produce Nsubstituted 2ABIs of pharmacological interest. Some commentaries about their biological activity were included.

Metal-Organic Frameworks (MOFs), a class of inorganic-organic hybrid materials, have been at the center of material science for the past three decades. They are synthesized by metal ions and organic linker precursors and have become very potential materials for different applications ranging from sensing, separation, catalytic behaviour to biomedical applications and drug delivery, owing to their structural flexibility, porosity and functionality. They are also very promising in heterogeneous catalysis for various industrial applications. These catalysts can be easily synthesized with extremely high surface areas, tunable pore sizes, and incorporation of catalytic centers via post-synthetic modification (PSM) or exchange of their components as compared to traditional heterogeneous catalysts, which is the preliminary requirement of a better catalyst. Here, in this review, we have presented the history of MOFs, different synthesis procedures, and MOFcatalysed reactions; for instance, coupling reactions, condensation reactions, Friedel-Crafts reaction, oxidation, etc. Special attention has been given to MOFs containing different catalytic centers, including open metal sites, incorporation of catalytic centers through PSM, and bifunctional acidbase sites. The important role of catalytic centers present in MOFs and reaction mechanisms have also been outlined with examples.

Aims: We have established this paper to recommend a novel way for the preparation of carbohydrates encompassing a 1,2,3-triazole motif that was prepared using an efficient click chemistry synthesis. Background: The SARS-CoV-2 coronavirus epidemic continues to spread at a fast rate worldwide. The main protease (Mpro) is useful target for anti-COVID-19 agents. Triazoles are frequently found in many bioactive products, such as coronavirus inhibitors. Objective: Click reactions are facilitated via the activation of copper nanoparticles, different substrates have been tested using this adopted procedure given in all cases, in high yields and purity. Other interesting comparative docking analyses will be the focus of this article. Calculations of quantitative structure-activity relationships will be studied. Methods: Copper nanoparticles were produced by the reaction of cupric acetate monohydrate with oleylamine and oleic acid. To a solution, 5-(azidomethyl)-2,2,7,7-tetramethyltetrahydro-5Hbis([ 1,3]dioxolo)[4,5-b:4',5'-d]pyran 2 (200 mg, 0.72 mmol, 1 eq.) in toluene (15 mL) was added into a mixture of N-(prop-2-yn-1-yl)benzamide derivatives 1a-d (1.5 eq.) and copper nanoparticles (0.57 mg, 0.036 mmol, 0.05 eq.). Results: A novel series of 1,2,3-triazole carbohydrate skeletons were modeled and efficiently synthesized. Based on the observations, virtual screening using molecular docking was performed to identify novel compounds that can bind with the protein structures of COVID-19 (PDB ID: 6LU7 and 6W41). We believed that the 1,2,3-triazole carbohydrate derivatives could aid in COVID-19 drug discovery. Conclusion: The formations of targeted triazoles were confirmed by different spectroscopic techniques (FT-IR, 1H NMR, 13C NMR, and CHN analyses). The docking scores of the newly synthesized triazole are attributed to the presence of hydrogen bonds together with many interactions between the ligands and the active amino acid residue of the receptor. The comparison of the interactions of the drugs, remdesivir and triazole, in the largest pocket of 6W41 and 6LU7 is also presented.

Background: In this current work, a new synthesis strategy was developed to obtain 1,3,4-trisubstituted pyrazoles derivatives. Methods: A series of 1,3,4-trisubstituted pyrazoles have been prepared via 1,3-dipolar cycloaddition reaction of 3-phenylsydnones with a variety of alkenes derivatives, symmetric and non-symmetric alkynes derivatives, N-phenyl-maleimide, N-benzylmaleimides, and maleic anhydride under conventional manner. Results: Moreover, in this work, it has been demonstrated that the 4-bromopyrazole intermediates can be further functionalized by a combination of Suzuki-Miyaura crosscoupling reactions with aryl-boronic acids and N-arylation reactions of anilines. Conclusion: In summary, we have developed a new method to obtain 1,3,4 triarylated pyrazoles through 3-phenylsydnone 1,3-dipolar cycloadditions. By comparing the different reactions, it is apparent that high temperatures and xylene as solvent are key to achieving pyrazoles derivatives. The best yields were observed for symmetric and non-symmetric alkynes as dipolarophiles.

Background: 1,3-Thiazolidin-4-ones are heterocycles whose importance in the pharmaceutical market has already been established. Many of these synthetic derivatives, which contain a thiazolidinone nucleus, are currently used in various commercial formulations or are already in clinical trials for the treatment of disease for their anticonvulsant, antihypertensive and antidiabetic activities in addition to their activity against Streptomyces. 1,3-Thiazolidin-4-ones are produced mainly by cyclo condensation between an imine (generated in situ by the reaction of an aldehyde with an amine) and α-mercaptoacetic acid, known as the MALI (Mercaptoacetic Acid Looking Imine) reaction. Objective: A solvent-free methodology was developed to synthesize a 1,3-thiazolidin-4-one family by the MALI reaction. An apparatus was developed to grind a solid-liquid mixture of anilines, benzaldehydes and thioglycolic acid to activate the reaction. This apparatus was named MGRE (mechanical grinding reaction equipment). Methods: Substituted aniline 2 (4 mmol), substituted benzaldehyde 1 (4 mmol) and thioglycolic acid 3 (12 mmol) were placed in a mortar. The reagents were macerated using the MGRE at room temperature for a specified time period. At the end of the reaction, the product was poured into ice, the precipitate formed was neutralized (with 5% NaHCO3), and the solution was extracted in ethyl acetate and dried in MgSO4. The solid was recrystallized from MeOH/H2O. Results: The developed MGRE is a modification of a rod used in a mechanical stirrer. This adaptation is inexpensive and simple in construction, and it enables reactions to occur over long periods of time that would be exhaustive for manual grinding. Fifteen (1,3) thiazolidin-4-ones were produced. The products were synthesized using the solvent-free MALI-MGRE procedure. Conclusions: The MALI-MGRE methodology developed to produce 1,3-thiazolidin-4-ones showed a good reaction scope, has an easy work-up and is solvent-free. Consequently, MALI-MGRE is classified as a green methodology. An innovation of this study is the construction of the MGRE, which involves modifying the rod in a mechanical stirrer. The equipment is easy and inexpensive to construct and may be useful for various reactions involving grinding.