Journal of Heterocyclic Chemistry最新文献

A novel [4+2] annulation reaction between o-acylamino-aryl MBH carbonates and isatylidene malononitriles has been successfully developed. This methodology exhibits excellent substrate tolerance, affording a series of spiro[indolin-3,2′-quinoline] framework compounds with yields up to 98%. The scalability of the reaction is also noteworthy, as evidenced by the 95% yield of the final product upon a 50-fold scale-up.

Many molecules called coumarins with very varied biological activities and widely used in the food, pharmaceutical, cosmetic, and medical industries. Their structure has a significant impact on their biological activity and their possible applications. Advanced synthesis frequently leads to an increase in the production of various chemical wastes. The amount of hazardous organic substances used and produced is reduced by the application of environmentally friendly synthesis techniques. Numerous techniques are employed in green chemistry, including the use of ionic liquids and deep eutectic solvents, solvent-free synthesis, mechanical synthesis, multicomponent reactions, ultrasound, and microwaves. These green synthesis techniques have been successfully applied to all common condensation reactions for the synthesis of coumarin, including the Perkin, Knoevenagel, Pechmann, Kostanecki-Robinson, and Reformansky reactions. These methods not only reduce the use and production of toxic chemicals, but also improve the yield, purity, and energy consumption of the product. This review summarizes the methods of microwave synthesis of coumarin derivatives, as well as their biological activities.

CO₂ is a significant greenhouse gas, and is considered as a copious renewable carbon reagent. From a synthetic perspective, it can be used as a sustainable and substitute C1 building block because of its nontoxic, nonflammable, and abundant nature. The transformation of a wide range of organic molecules with CO₂ into numerous efficient commodities is a defining feature of recent success in this sector. Because of its numerous applications, photocatalysts and visible light-mediated synthesis of carbamates and cyclic carbonates using CO₂ have drawn a lot of interest from researchers. This mini review mainly focusses on the different one-pot reactions that are proven to be efficacious for chemical fixation of CO₂ in producing industry-based compounds of carbamates and carbonates with the creation of CO, CH, CC, and CN bonds.

Three novel heterocyclic host based on diaryl ketone-tethered 1,5-diazocines were designed and synthesized for applications in phosphorescent organic light-emitting diodes (PhOLEDs). The hosts were derived by anchoring the naphthyl ketone (TBN), anthryl ketone (TBA), and phenanthryl ketone (TBP) to the 1,5-diazocine core. The materials were successfully characterized using spectroscopic techniques. TBN and TBP exhibited low external quantum efficiency of 1.5% and 1.9% when explored as hosts in PhOLED devices. Among the series, TBP exhibited the highest luminance of 4160 cd/m², maximum luminance efficiency of 6.3 cd/A, and power efficiency of 3.21 lm/w, when doped with Ir(ppy)₃ in PhOLED. Nevertheless to our surprise, TBA manifested the lowest device performance than other TBs as a host due to low carrier mobility caused by a highly twisted structure as deciphered from the comparative analysis of single-crystal structure that could impede carrier transport crucial for efficient electroluminescence. The outcomes of electroluminescence were validated and explained with analysis of single-crystal structure, and also with the aid of density functional theory.

Succinate dehydrogenase inhibitor (SDHI) is an important fungicide to control grain diseases. For this reason, a series of novel pyrazole-4-carboxamide derivatives with an N-methoxy group were designed and synthesized. All the target compounds were characterized by ¹H NMR, ¹³C NMR, and HRMS. The compound 3c was further confirmed by X-ray diffraction, which crystallized in the triclinic system, space group P-1, Z = 2. The fungicidal activity results indicated that most of these compounds possessed good activity against Sclerotinia sclerotiorum at 50 ppm. Especially, compound 3h exhibited the best activity with the EC₅₀ is 7.80 μg/mL, which is comparable with the positive control bixafen (EC₅₀ = 6.70 μg/mL). Furthermore, the physicochemical properties, molecular docking simulation, ADMET analyses, DFT of compounds 3h, 3k and two commercial SDHIs, isoflucypram and pydiflumetofen, were investigated in this study.

A novel series of pyrimidine sulfonamide derivatives was synthesized through a strategic approach involving the creation of substituted dihydropyrimidinyl-benzenesulfonamides and subsequent transformation into their chlorinated analogues. These compounds were then subjected to reactions with various amines and phenols, yielding unique substituted sulfapyrimidines. These novel structures integrated essential pharmacophores such as phenols, secondary amines, and benzenesulfonamide moieties, each contributing distinct biological potencies, chemical reactivity, and enhanced pharmacological features. In the pursuit of effective anticancer agents, the newly substituted pyrimidine sulfonamides were characterized using spectroscopic and x-ray diffraction techniques. The compounds were evaluated for their anti-proliferative potency against the NCI 60-cell lines panel, revealing that compound 7c exhibited significant growth inhibition across multiple cancer cell lines. Further assessment through MTT assay on HCT-116 and MCF-7 cell lines demonstrated cytotoxicity, while cell cycle analysis of MCF-7 cells treated with compound 7c revealed arrest at the S phase. Moreover, the effect of 7c on programmed cell death was evaluated using the Annexin V/PI apoptosis assay. The observed promising activity positions these pyrimidine-based scaffolds as potential candidates for future drug development, offering valuable insights for medicinal chemists engaged in the design and synthesis of anticancer drugs.

Five new benzannulated steroid spiroketals were synthesized by Pd-catalyzed spiroketalization of 5α and 5β-alkynediols derived from stigmasterol and sitosterol. The detailed nuclear magnetic resonance (NMR) and X-ray characterization of the newly obtained spiroketals are presented. While the obtained compounds showed null or very low cytotoxicity, two of them inhibited more than 60% of the nitrous oxide production in J774A.1 macrophages stimulated with LPS, showing promising properties as anti-inflammatory agents.

Pyrazole derivatives are strategic structural motifs due to their proven utility in preparing chemicals in biological, pharmaceutical, photophysical, technological, and industrial fields; therefore, syntheses of pyrazole-containing compounds are highly desirable. Some nitrogen-rich pyrazoles, specifically nitrated derivatives posing high density and moderate thermal stability, have been used as energetic compounds since a high amount of energy is stored in their structures that can be released quickly with high detonation power under external stimuli (i.e., thermal, impact, and friction). These compounds have good capacity and sensitivity in explosives, propellants, and pyrotechnics applications in eco-friendly ways. Therefore, this contribution focuses on recent and illustrative examples regarding the (i) synthesis and reactivity of pyrazoles, especially works of the last decade, highlighting works on (ii) applications in energetic compounds to analyze their scope.

A total of 48 tetrahydrooxazolo-[5′,4′:4,5]pyrimido[1,2-a]azepinones were designed and synthesized from a scaffold hopping approach. All compounds were confirmed by analysis using ¹H NMR, ¹³C NMR, and HRMS techniques. The synthesized compounds were evaluated against the human cancer cell lines (HeLa, MCF-7, A549) in vitro, and the structure–activity relationships were summarized. The compound E43 exhibited the best inhibitory activity against HeLa, MCF-7, A549, displaying IC₅₀ values of 1.48 ± 0.13, 3.01 ± 0.09, and 5.11 ± 0.13 μM. Molecular docking indicated that compound E43 may bind to protein (PDB:6FEX) via hydrogen bond and π stacking. Further, molecular dynamics simulations indicated a relatively low binding free energy (−40.06 kJ·mol⁻¹) of compound E43 with protein. In conclusion, these findings suggested that E43 is promising as a potential novel anticancer drug candidate worthy of further investigation.

For the first time, the interaction of perfluoro-1,4-naphthoquinone with various 5-aminopyrazoles was investigated. It was shown that three types of products can be obtained depending on the structure of starting aminopyrazole. For all examples, the substitution of one fluorine atom in quinone moiety was observed. Wherein, in most cases, the starting aminopyrazoles act as a C-nucleophile leading to 2-(5-aminopyrazol-4-yl)-3,5,6,7,8-pentafluoronaphthalene-1,4-diones. At the same time substrates unsubstituted at ring nitrogen atom regiospecifically react at aminogroup resulting in the formation of 2,5,6,7,8-pentafluoro-3-((pyrazol-5-yl)amino)naphthalene-1,4-diones. Besides that, the absence of steric hindrance in the pyrazole unit allowed us to direct the process at nitrogen atom in Position 2 and synthesize zwitter-ionic 3-(5-aminopyrazol-2-ium-2-yl)-5,6,7,8-tetrafluoro-1,4-dioxo-1,4-dihydronaphthalen-2-olates. The structures of two types of obtained products were confirmed by x-ray analysis.