Search Results (43)

Heterocycles—cyclic compounds containing at least one non-carbon heteroatom (e.g., N, O, S)—are fundamental in medicinal chemistry due to their influence on a drug’s physicochemical and biological properties. They improve solubility, bioavailability, and facilitate molecular recognition through their electronic and hydrogen-bonding features. These properties make them indispensable in drug design. This study focuses on the synthesis of a key heterocyclic intermediate: benzyl-N-[4-(2-hydroxyethyl)-1,3-thiazol-2-yl]carbamate. This molecule incorporates a thiazole ring, known for its rigidity and electronic properties, that enhances target interactions. The 2-position bears a Cbz-protected amine, enabling orthogonal deprotection, while the 4-position features a hydroxyethyl side chain, providing a handle for further chemical modifications via nucleophilic substitution. Herein, we report the successful synthesis of this intermediate along with its full ¹H and ¹³C NMR spectra, melting point, and crystal structure, confirming its identity and purity. Full article

In this study, a C-C bond-linked triazole-fused oxadiazole energetic compound, 4-amino-5-(4-amino-1,2,5-oxadiazol-3-yl)-2,4-dihydro-3H-1,2,4-triazol-3-one (1), was successfully designed and efficiently synthesized. Following nitration, a functional group-modified nitramine energetic compound (2) was obtained, and its energetic ionic salt (3) was further prepared. A comprehensive characterization of the structures of these three compounds was conducted, resulting in the successful elucidation of the single-crystal structures of compound 2·Ca²⁺·6H₂O and compound 3·MeOH. Compound 2 exhibited a positive formation enthalpy (56.2 kJ·mol⁻¹) and moderate mechanical sensitivity (FS = 120 N, IS = 12 J). Due to the presence of the nitramine group, compound 2 exhibited a relatively low thermal decomposition temperature (T_dec = 94 °C). However, the thermal stability of compound 3 was significantly improved (T_dec = 233 °C), which is attributed to salt formation. Compound 3 exhibits a positive formation enthalpy (121.0 kJ·mol⁻¹), along with excellent detonation performance (D = 8120 m·s⁻¹, P = 32.1 GPa) and reduced mechanical sensitivity (FS = 224 N, IS = 24 J). Therefore, the multi-heterocyclic compound, joined via C-C bond linkage, demonstrates outstanding performance, offering a new avenue for the design and synthesis of energetic materials. Full article

N-Heterocyclic carbenes (NHCs) have been widely utilized over the past three decades due to their broad applications, yet synthetic methods for their preparation remain limited. A promising approach for NHC generation involves the thermolysis of NHC adducts. Herein, we report the synthesis of NHC pentafluorobenzene adducts featuring an o-carboranyl group in the backbone (2), which, unlike previously studied systems, resists thermal decomposition. Density functional theory (DFT) calculations were used to investigate the discrepancy, revealing that the decomposition reaction is kinetically controlled. For widely studied NHC systems like IMes and SIMes, the activation barriers were calculated to be 246.3 kJ/mol and 267.3 kJ/mol, respectively, aligning with reactions requiring heating. In contrast, the o-carborane system exhibited a significantly higher barrier of 320.5 kJ/mol, primarily due to the structural influence of the o-carborane backbone. Further analysis indicates that delocalization of π-electrons from the backbone into the NHC’s p-orbitals lowers the activation barrier, whereas delocalization into an exo-NHC ring increases it. These findings provide new insights into the thermal generation of NHCs and we hope it can offer guidance for future NHC design and synthesis. Full article

Polystyrene-supported chiral hydroxyamide-functionalized benzimidazolium chloride was synthesized by reacting Merrifield resin with a substituted-azole derived from (S)-leucinol. The combination of [IrCl(cod)]₂ and the resulting polymer-supported N-heterocyclic carbene (NHC) ligand precursor catalyzed the enantioselective reduction of ketones using (EtO)₂MeSiH under heterogeneous reaction conditions via a pre-mixing reaction procedure. Additionally, the solid-state resin could be easily recovered through simple filtration and the catalyst system’s reusability was evaluated. Full article

The Konduyak gold–quartz–sulfide deposit is one of the most promising gold mines in the Ayakhta gold ore cluster on the Yenisei ridge. This article is devoted to the study of the composition of the volatile compounds in the ore-forming fluid, since this is one of the key aspects in understanding the conditions of deposit formation. The compositions of the fluids that formed quartz and pyrite in the deposit ore zone were determined using Raman spectroscopy and pyrolysis-free gas chromatography–mass spectrometry. The study of the fluid inclusions in the minerals showed that complex C-H-O-S-N multi-component fluids formed the quartz–sulfide ore zones. A range of 232 to 302 various volatile compounds were found in the fluids. The mineralizing fluids mainly consist of H₂O (14.25–96.02 rel. %) and CO₂ (2.07–54.44 rel. %). A high SO₂ content (14.60–44.95 rel. %) is typical of fluids trapped by pyrites. Moreover, a wide range of hydrocarbons (oxygen-free aliphatic, cyclic, heterocyclic, and oxygenated) and nitrogenated and sulfur compounds were found among the volatiles in the fluid. The variable H/(H + O) ratios, from 0.51 to 0.81, and CO₂/(CO₂ + H₂O) ratios, from 0.02 to 0.56, indicate changes in the redox conditions during ore formation. Full article

The six-membered N,S-heterocyclic 1,3-thiazines and their derivatives are widely acknowledged as pharmaceutical molecules with a wide range of biological activities. In this study, we developed a unique thiol-involved cascade reaction that enables the efficient construction of the 5,6-dihydro-4H-1,3-thiazine scaffold through consecutive intermolecular thiol-isothiocyanate and intramolecular thiol-halogen click reactions. Structurally diverse 2-mercapto dihydrothiazines including three antitumour candidates of bis-dihydrothiazines were readily obtained in high yields from the readily available thiols and 3-chloroisothiocyanate in the green solvent EtOH/H₂O (1:1) using K₂CO₃ (0.6 equiv.) as the base. Between the two synthesis procedures investigated, the microwave-assisted reaction generally behaved more efficiently than that under routine heating conditions. Furthermore, DFT calculation confirmed the sequential addition–substitution mechanism. This cascade C–S coupling reaction methodology offers several advantages, including rapid completion, high reliability, easy purification, and benign conditions. Full article

This study focuses on synthesizing a new series of isoxazolinyl-1,2,3-triazolyl-[1,4]-benzoxazin-3-one derivatives 5a–5o. The synthesis method involves a double 1,3-dipolar cycloaddition reaction following a “click chemistry” approach, starting from the respective [1,4]-benzoxazin-3-ones. Additionally, the study aims to evaluate the antidiabetic potential of these newly synthesized compounds through in silico methods. This synthesis approach allows for the combination of three heterocyclic components: [1,4]-benzoxazin-3-one, 1,2,3-triazole, and isoxazoline, known for their diverse biological activities. The synthesis procedure involved a two-step process. Firstly, a 1,3-dipolar cycloaddition reaction was performed involving the propargylic moiety linked to the [1,4]-benzoxazin-3-one and the allylic azide. Secondly, a second cycloaddition reaction was conducted using the product from the first step, containing the allylic part and an oxime. The synthesized compounds were thoroughly characterized using spectroscopic methods, including ¹H NMR, ¹³C NMR, DEPT-135, and IR. This molecular docking method revealed a promising antidiabetic potential of the synthesized compounds, particularly against two key diabetes-related enzymes: pancreatic α-amylase, with the two synthetic molecules 5a and 5o showing the highest affinity values of 9.2 and 9.1 kcal/mol, respectively, and intestinal α-glucosidase, with the two synthetic molecules 5n and 5e showing the highest affinity values of −9.9 and −9.6 kcal/mol, respectively. Indeed, the synthesized compounds have shown significant potential as antidiabetic agents, as indicated by molecular docking studies against the enzymes α-amylase and α-glucosidase. Additionally, ADME analyses have revealed that all the synthetic compounds examined in our study demonstrate high intestinal absorption, meet Lipinski’s criteria, and fall within the required range for oral bioavailability, indicating their potential suitability for oral drug development. Full article

A series of novel salts of heterocyclic polyamines with 5-sulfosalicylic acid (C₄H₇N₄⁺)(C₇H₅O₆S⁻)∙2(H₂O) (1), (C₄H₆ClN₄⁺)(C₇H₅O₆S⁻)∙H₂O (2), (C₅H₈N₃⁺)(C₇H₅O₆S⁻)∙H₂O (3), (C₅H₇N₆⁺)(C₇H₅O₆S⁻)∙H₂O (4), (C₆H₁₄N₂²⁺)(C₇H₄O₆S²⁻)∙H₂O (5), and (C₁₄H₁₉N₂⁺)(C₇H₅O₆S⁻) (6) have been successfully synthesized. Their crystal structures have been determined by single-crystal X-ray diffraction. Overall, compounds adopt a layered structure with aminium cations and 5-sulfosalicylic anions linked via water molecules. The solid-state architectures of these compounds are dominated by O(N,H)-H⋯O and N-H⋯N hydrogen bonds and stabilized by weak interconnects. C-Cl⋯π and S-O⋯π interactions, apart from π⋯π and C-H(O)⋯π, were reported. Diverse approaches were used to study the effect of substituents in the polyamines in solid-state arrangement. A Hirshfeld surface analysis, with associated 3D Hirshfeld surface maps and 2D fingerprint plots, molecular electrostatic potential, and energy frameworks were used to comprehensively investigate the nature and hierarchy of non-covalent interactions and inspect supramolecular differences. The contact enrichment ratio calculations provided deeper insight into the propensity of interconnects to influence crystal packing. The evaluation of the effects of H-bonding synthons resulting from different substituents in the polyamines on self-assemblies is also presented. In the context of crystal engineering, a specific intramolecular synthon via O-H⋯O observed in nearly all crystals can be employed in the pseudo-cyclic replacement strategy in the design of new molecules. Full article

A new, eco-friendly process utilising the green solvent propylene carbonate (PC) has been developed to perform N-alkylation of N-, O- and/or S-containing heterocyclic compounds. PC in these reactions served as both the reagent and solvent. Importantly, no genotoxic alkyl halides were required. No auxiliary was necessary when using anhydrous PC. Product formation includes nucleophilic substitution with the concomitant loss of water and carbon dioxide. Substrates prepared, including the newly invented PROTAC drugs, are widely used. Full article

The wide range of biological processes and functions that benzimidazole moieties can be used for makes them very interesting synthetic molecules. A novel class of scaffolds for benzimidazole heterocycles has been successfully constructed in the present study and synthesized by using the starting material of O-phenylenediamine derivatives (1a–c). The 1-methyl-2-(methylthio)-1H-benzo[d]imidazole derivatives (3a–c) have been synthesized as intermediate compounds by treating the precursors (1a–c) with carbon disulfide followed by N- and S-methylation with iodomethane and anhydrous potassium carbonate. In the latter step, the intermediate molecules were converted into benzimidazole-containing methyl-piperazine (4a–c), piperazin-ol tethered benzimidazoles (5a–c), and phenylpiperazine holding benzimidazoles (6a–c). The structures assigned to target compounds have been analyzed and confirmed via IR, NMR, and MS analysis. The antibacterial, anthelmintic, and anticancer properties of the target compounds were examined. The biological study showed that the compounds 6b, 4c, and 5a emerge as excellent antibacterial, antifungal, and anthelmintic agents, respectively, whereas heterocycle 6a showed excellent anticancer activity against hepatocyte-derived cell line HUH7, as well as the MCF7 breast cancer cell line with IC₅₀ values of 6.41 and 9.70 µg/mL, respectively. The discovery of a novel class of hetero compounds with multiple hetero moieties that may aid in medication design is also highlighted in this study. Full article

An efficient regioselective approach to novel functionalized bis(isoxazoles) with a variety of aromatic and aliphatic linkers was elaborated, based on the heterocyclization reaction of electrophilic alkenes under the treatment with tetranitromethane-triethylamine complex affording 3-EWG-5-nitroisoxazoles. The subsequent S_NAr reactions of 5-nitroisoxazoles with various O,O-, N,N- and S,S-bis(nucleophiles) provide a wide range of bis(isoxazole) derivatives in good isolated yields. Employing an elaborated method, a series of novel bis(3-EWG-isoxazoles) as the promising allosteric modulators of AMPA receptors were designed and synthesized. The effect of the compounds on the kainate-induced currents was studied in the patch clamp experiments, revealing modulator properties for several of them. The best positive modulator potency was found for dimethyl 5,5′-(ethane-1,2-diylbis(sulfanediyl))bis(isoxazole-3-carboxylate), which potentiated the kainate-induced currents in a wide concentration range (10⁻¹²–10⁻⁶ M) with maximum potentiation of 77% at 10⁻¹⁰ M. The results were rationalized using molecular docking and molecular dynamics simulations of modulator complexes with the dimeric ligand-binding domain of the GluA2 AMPA receptor. The predicted physicochemical, ADMET, and PAINS properties confirmed that the AMPA receptor modulators based on the bis(isoxazole) scaffold may serve as potential lead compounds for the development of neuroprotective drugs. Full article

The reactivity of the racemic N-heterocyclic stannylene [{MeHCN(^tBu)}Sn] (1) with the chalcogenide elements O₂, S, Se, and Te has been investigated. In the case of the reaction of 1 with molecular oxygen, the cyclic tristannoxane complex [{MeHCN(^tBu)}₂Sn(μ-O)]₃ (3) was isolated and characterised. NMR studies (¹H, ¹³C, and ¹¹⁹Sn) show the formation of D₃- and C₂- symmetric assemblies. The reaction of 1 with S, Se, and Te, respectively, yielded the cyclo-distannachalcogenide complexes, [{MeHCN(^tBu)}₂Sn(μ-E)]₃ (4: E = S, 5: E = Se, 6: E = Te), again with multinuclear NMR studies proving the formation of C₂- and C_s-symmetric assemblies. Single crystal X-ray diffraction studies have been used to elucidate the molecular structures of the products of oxidative addition, 3, 4, 5, and 6. Full article

In this study, we investigated the abilities of nitrogen and sulfur heterocyclic carbenes of benzotriazole, 2-mercaptobenzothiazole, 8-hydroxyquinoline, and 3-amino-1,2,4-triazole-5-thiol regarding adsorption on an Al-Mg-Si alloy toward corrosion inhibition of the surface. Al-Si(14), Al-Si(19), and Al-Si(21) in the Al-Mg-Si alloy surface with the highest fluctuation in the shielding tensors of the “NMR” spectrum generated by intra-atomic interaction directed us to the most influence in the neighbor atoms generated by interatomic reactions of N → Al, O → Al, and S → Al through the coating and adsorbing process of Langmuir adsorption. The values of various thermodynamic properties and dipole moments of benzotriazole, 2-mercaptobenzothiazole, 8-hydroxyquinoline, and 3-amino-1,2,4-triazole-5-thiol adsorbed on the Al-Mg-Si increased by enhancing the molecular weight of these compounds as well as the charge distribution between organic compounds (electron donor) and the alloy surface (electron acceptor). Finally, this research can build up our knowledge of the electronic structure, relative stability, and surface bonding of various metal alloy surfaces, metal-doped alloy nanosheets, and other dependent mechanisms such as heterogeneous catalysis, friction lubrication, and biological systems. Full article

The synthesis of heterocycles is a fundamental area of organic chemistry that offers enormous potential for the discovery of new products with important applications in our daily life such as pharmaceuticals, agrochemicals, flavors, dyes, and, more generally, engineered materials with innovative properties. As heterocyclic compounds find application across multiple industries and are prepared in very large quantities, the development of sustainable approaches for their synthesis has become a crucial objective for contemporary green chemistry committed to reducing the environmental impact of chemical processes. In this context, the present review focuses on the recent methodologies aimed at preparing N-, O- and S-heterocyclic compounds in Deep Eutectic Solvents, a new class of ionic solvents that are non-volatile, non-toxic, easy to prepare, easy to recycle, and can be obtained from renewable sources. Emphasis has been placed on those processes that prioritize the recycling of catalyst and solvent, as they offer the dual benefit of promoting synthetic efficiency while demonstrating environmental responsibility. Full article

Cascade reactions provide a straightforward access to many valuable compounds and reduce considerably the number of steps of a synthetic sequence. Among the domino and multicomponent processes that involve alkynes, the cascade reaction between alkynoic acids and C-, N-, O- and S-aminonucleophiles stands out as a particularly powerful tool for the one-pot construction of libraries of nitrogen-containing heterocyclic compounds with scaffold diversity and molecular complexity. This reaction, based on an initial metal-catalyzed cycloisomerization that generates an alkylidene lactone intermediate, was originally catalyzed by gold(I) catalysts, along with silver salts or Brönsted acid additives, but other alternative metal catalysts have emerged in the last decade as well as different reaction media. This review examines the existing literature on the topic of metal-catalyzed cascade reactions of acetylenic acids and dinucleophiles and discusses aspects concerning substrate/catalyst ratio for every catalyst system, nature of the aminonucleophile involved and substrate scope. In addition, alternative solvents are also considered, and an insight into the pathway of the reaction and possible intermediates is also provided. Full article