Current Organic Chemistry - Volume 26, Issue 19, 2022

Due mainly to their structural diversities, pharmacological, electrochemical, and photophysical properties, the metal synthesis pyrazole and benzimidazole complexes were extensively designed and developed. The nitrogen-containing ligands playing an important role in coordination chemistry contain a wide variety of heterocyclic systems possessing one or more nitrogen atoms as electron donors, such as pyridine, isoxazole, pyrazole, 1,2,4- triazole, 1,3,5-triazine, quinoline, quinoxaline and benzothiazole. The structure of all ligands and the corresponding metal complexes are established using elemental analysis, infrared spectroscopy, NMR spectroscopy, mass spectrometry, single-crystal X-ray diffraction, thermogravimetric differential thermal analysis, static, magnetic susceptibility measurements, electron paramagnetic resonance spectroscopy (EPR), UV-Vis spectroscopy, and conductivity measurements.In this review, we report the synthesis and the chelating reactions of several heterocyclic ligands with various metals such as transition metals and lanthanides. The photophysical and photochemical properties of the metal complexes will also be presented and discussed.

It has been established on the basis of reported research that benzimidazoles and their analogs are active scaffolds. Benzimidazole is a benzofused imidazole compound that is present in several marketed molecules with a wide range of uses that established its importance in pharmaceutical sectors and industry. Drugs with a benzimidazole nucleus have unique structural characteristics and an electron-rich environment that allows them to attach to a variety of physiologically significant sites and produce a variety of actions. The development of benzimidazole heterocyclic molecules as antihistaminic (H1-receptor antagonist, for example, bilastine; 5-HT3 antagonist, for example, leri-setron); antimicrobial (antibiotic, for example, ridinilazole); antiulcer (proton pump inhibitor (PPI), for example, ilaprazole); antihypertensive (calcium channel blocker, for example, mibefradil); and drugs used to treat cancer include those that are antiparasitic (specifically anthelmintic, such as fubendazole), antipsychotic (D2 receptor antagonist, such as clopimozide), analgesic (opioid analgesic, such as clonitazene), and phosphodiesterase inhibitor (PDE3 inhibitor, such as adibendan). Due to its broad applications, scientists are continuously enthralled by benzimidazoles and their derivatives to study their chemistry. Several synthesis strategies can prepare benzimidazole or its derivatives and the focus will always be on new, greener, and more economical ways for its synthesis. Among all methods, catalytic cyclization, catalytic coupling, and catalytic reactions are the most used approaches for the synthesis of benzimidazoles and their analogs. The present review entitled various synthetic approaches for synthesizing benzimidazole from 2009 to 2021 and its derivatives, which will be very useful to researchers for developing benzimidazole moieties.

Heterocycles having nitrogen and sulphur atoms attract chief attention due to their importance in diverse fields, especially in medicinal chemistry and pharmaceutical industry. Among those, 2-aminothiazole, one of the most flexible and pervasive heterocyclic scaffolds found in many natural and synthetic products, exhibits a wide variety of biological activities. A one-pot method for the synthesis of 2-aminothiazoles through Cu(II)-iodine-catalyzed Hantzsch condensation has been achieved for the first time. This novel green methodology facilitates the formation of a broad range of 2-aminothiazole derivatives utilizing catalytic quantities of Cu(II) salts and iodine, incorporating various methyl aryl ketones and thiourea as substrates. This novel strategy involves a Hantzsch-type condensation between thiourea and in situ generated α-iodoketones, formed from the reaction of methyl aryl ketones and iodine. The present protocol reveals PEG-400 as the best solvent, which furnishes moderate to good yields of the desired 2- aminothiazole derivatives. The addition of a catalytic quantity of copper acetate ensures the continuous availability of iodine for several catalytic cycles, as copper(II) allows the oxidation of iodide to iodine. The feasibility of this novel route is studied with electron-withdrawing, electron-donating and halo-substituted derivatives of methyl aryl ketones with thiourea to confirm the functional group compatibility of the reaction. Moreover, this efficient strategy evades the direct use of noxious and lachrymatory α–halocarbonyls as reaction substrates and strong oxidants. Using a catalytic quantity of iodine in the reaction makes the separation of the desired products much easier by reducing the amount of unwanted side-products than utilizing a stoichiometric amount of iodine.

An efficient strategy for the synthesis of pyrido[2,3-b]indoles through VCl3-catalyzed cascade cyclization reactions of N,N-dimethyl enaminones or chalcones with 2-(2-aminophenyl)- acetonitrile under mild reaction conditions was developed. This method features many advantages, such as readily available starting materials, good substrate, good functional group tolerance, and good yields. A plausible reaction mechanism was provided. Moreover, the high yields of N-unprotected substrates made this reaction system extremely advantageous with currently known methods.

Hypericum oblongifolium is a potent source of bioactive constituents. A series of pharmacological properties, ranging from wound healing and antiseptic to antiviral, antiinflammatory, anticancer, and apoptosis-inducing activities have been associated with this plant. The current research project was designed to investigate the new secondary metabolites in H. oblongifolium having excellent pharmaceutical potential. In the present investigation two new cholestane-type steroids, hyperinoate A (1) and hyperinoate B (2) were isolated from a chloroform soluble fraction of the whole plant of H. oblongifolium. Structures of isolated new compounds were elucidated based on spectroscopic data including 1D (¹HNMR, ¹³CNMR) and 2D (HMBC, COSY, NOESY) NMR and mass spectrometry (EIMS, HREIMS) data. After structure elucidation, new compounds were named 6α-hydroxy-14α-methyl Cholestan-3-ylacetate and 6α,25-dihydroxy-14α-methyl Cholestane-3-yl-acetate. Both steroids showed promising inhibitory activity against lipoxygenase (LOX) and acetylcholinesterase (AChE) enzymes. Especially hyperinoate A (1) inhibited the lipoxygenase (LOX) enzyme with IC50 41.7± 0.15 μM whereas Baicalein (positive control) had IC50 2.20 ± 0.04 μM. Similarly, Hyperinoate B (2) (56.3 ± 0.33 μM) showed moderate inhibition compared to Galantamine (positive control) 5.38 ± 0.54 μM. These results were validated with in-silico molecular docking investigations. The binding affinity of hyperinoate A (1) (-9.2 Kcal/mol) against LOX-5(PDB ID 3V99) showed moderate inhibition as compared to baicalein (positive control) (-7.7 Kcal/mol).The binding affinities of hyperinoate B (2) (-10.5 Kcal/mol) were close to galantamine (-10.6 Kcal/mol). All in-vitro and in-silico results revealed that both newly isolated compounds showed moderate inhibition against lipoxygenase (LOX) and acetylcholinesterase (AChE) enzymes.

Aim and Objective: To develop a ruthenium-catalyzed method to prepare metanitration containing 1,2,4-thiadiazoles with potential biological activity. Moreover, the current protocol should exhibit a relatively broad substrate scope and functional group compatibility. Materials and Methods: The best condition for the synthesis of nitration containing 1,2,4- thiadiazoles derivatives was carried out employing a mixture of 0.20 mmol of 1 (1a: 47.6 mg, 1b: 53.2 mg, 1c: 70.1 mg, 1d: 59.7 mg, 1e: 81.2 mg, 1f: 54.8 mg, 1g: 61.4 mg, 1h: 74.8 mg, 1i: 53.2 mg, 1j: 59.0 mg, 1k: 54.9 mg, 1l: 50.0 mg), Cu(NO3)2•3H2O (120.8 mg, 0.5 mmol), Ru3CO12 (9.6 mg, 7.5 mol %), TBAOAc (18.0 mg, 30 mol %), AgTFA (66.2 mg, 1.5 equiv), oxone (123.0 mg, 1.0 equiv), DCE (1.0 mL) placing in a Schlenk tube and stirred at 90 oC under air atmosphere for 36.0 h. Results: A series of 1,2,4-thiadiazoles containing compounds with potential biological activity were prepared in yield ranging from moderate to good under mild conditions, exhibiting a relatively broad substrate scope and functional group compatibility. Conclusion: We have developed a ruthenium-catalyzed 1,2,4-thiadiazoles-assisted regioselective meta-C-H nitration of arenes. This study provides a simple and efficient approach for synthesizing 1,2,4-thiadiazoles derivatives, yielding the nitration products in moderate to good yields. A mechanistic study indicated that a radical pathway might be involved in this transformation.