Journal of Heterocyclic Chemistry最新文献

Heteroaryl-1,2,4-triazine complexants are commonly utilized in separation science for the selective chelation of minor An from Ln in simulated high-level waste. To facilitate access to relevant chemical entities for hypothesis-driven inquiry toward improved separations performance, a synthetic method to construct various alkoxy-complexant derivatives was required. In this work, a convergent synthetic strategy for the production of 3,3′- and 4,4′-tetraalkoxy-bis-1,2,4-triazinyl-2,6-pyridines from readily available starting materials via a dealkylation/alkylation/condensation approach is described. Synthetic method development, substrate scope, preliminary solubility, and hydrolytic stability data in various process-relevant diluents are reported herein.

A practicable method is described for the synthesis of 3-acyl-pyrazolo[1,5-a]pyridines from N-aminopyridines and easily available enaminones via a [3+2] cycloaddition. The reactions proceed well with a broad scope, without using additive (base or oxidant).

2-Vinylanilines are readily accessible substrates, which are undoubtedly one of the best candidates for the construction of diversely nitrogen-containing heterocyclic compounds. Owing to the amine and alkenyl groups in their structures, these frameworks offer a facile, direct, and selective synthetic method. This review describes various cyclization reactions involving 2-vinylanilines catalyzed by transition metals, or under metal-free conditions.

Pyrimidine-based derivatives have attracted a lot of interest in heterocyclic chemistry due to its versatile structure and diverse biological activities. This study provides a comprehensive overview of synthetic strategy of different pyrimidine ring and highlights their biological importance. In this article, we start off by going through the fundamental procedures for the synthesis of pyrimidine scaffolds, including both conventional and contemporary synthetic techniques. These works cover a range of therapeutic domains, such as effects that are anticancer, antibacterial, antiviral, anti-inflammatory, antioxidant, antimalarial, and so on. Moreover, we have summarized with a discussion of future prospects and challenges in the field of pyrimidine heterocyclic chemistry. This thorough review is a significant resource for researchers in medicinal chemistry and related fields since it offers insightful information about the synthetic methods and biological applications of pyrimidine-based derivatives.

4-(3-(Dimethylamino)acryloyl)-5-methyl-N-phenyl-1-(p-tolyl)-1H-pyrazole-3-carboxamide was prepared via refluxing of 4-acetyl-5-methyl-N-phenyl-1-(p-tolyl)-1H-pyrazole-3-carboxamide with dimethylformamide dimethyl acetal. The target bipyrazoles were obtained from regioselective reaction of the latter enaminone with different hydrazonoyl halides at reflux in chloroform in the presence of trimethylamine. The regioselectivity was confirmed chemically upon refluxing with hydrazine hydrate in ethanol. The structures of the newly synthesized compounds were established on the basis of their elemental analyses and spectral data. The specified compounds were tested for antibacterial activity against gram-negative bacteria (Escherichia coli) and (Pseudomonas aeruginosa) and a gram-positive bacteria (Bacillus subtilis) and (Staphylococcus aureus) using disk diffusion method. Antibacterial studies revealed that compounds 8a, 10b, 10c, 11d, and 14b showed weak to moderate activity against the tested bacteria compared to ampicillin.

A series of pyrrolo[3,2-f]quinoxaline derivatives have been obtained by a three-component domino reaction of quinoxalin-6-amine, arylglyoxal monohydrates, and cyclic 1,3-dicarbonyl compounds in ethanol medium at 80°C catalyzed by acetic acid. The notable features of this synthesis are excellent regioselectivity, operational simplicity, relatively mild reaction conditions, and good yields.

A new series of tetrazole fused with 1,3,4-thiadiazole-2-amine (4a–j) moiety have been synthesized. A thorough characterization of each compound was carried out using mass spectrum data, FT-IR, ¹H, and ¹³C NMR studies. The antibacterial effectiveness of these prepared substances was assessed in vitro against Gram-(−) strains of P. aeruginosa and E. coli, as well as Gram-(+) strains of B. subtilis and S. aureus. Molecules 4f and 4h showed exceptional effectiveness against both types of strains when compared to the reference antibiotic Streptomycin. Moreover the evolution of the molecular docking (in silico) studies also helpful for all the synthesized compounds and reference amoxicillin. The investigation included a look at protein stability, APO-protein dynamics, and interactions. Using Molecular Dynamics (MD) simulations with Desmond Maestro version 11.3 for this inquiry, a potential lead molecule was found.

Angiotensin-converting enzyme inhibitors are widely used in treating arterial hypertension, acting on the renin-angiotensin-aldosterone system and controlling blood pressure. We present a novel, greener, and faster methodology to assess the 1,2,4-oxadiazol-5-one ring and perform molecular modifications to obtain angiotensin-converting enzyme (ACE) inhibitors using this heterocyclic core. Molecular docking simulations indicate that the tested compounds exhibited an affinity for the ACE binding site, with scores comparable to the commercial inhibitor lisinopril. However, in vitro assays revealed that the compounds were ineffective in inhibiting ACE activity. The lack of inhibition may be related to the compounds' more apolar nature. These results emphasize the importance of integrating computational and experimental approaches in developing new drugs, providing valuable insights for planning future studies to optimize the activity of synthesized compounds.

N-Alkyl-2-nitroanilines deoxygenated with tributylphosphine form intermediate 2-(alkylamino)aryliminophosphoranes, which were subjected, without isolation, to various cyclocondensation reactions with CS₂, CO₂, alkyl isocyanates, acyl chlorides, anhydrides, or esters. A simple, convenient, one-pot procedure provided derivatives of unsymmetrically substituted 1-alkylbenzimidazoles functionalized at C2 in good to excellent yields. The method does not require the use of metals, sensitive catalysts, or pressure.

The objective of this study is to synthesize novel heterocyclic scaffolds containing a thiophene moiety using easily accessible acetoacetamide as a key synthon. The reaction of acetoacetamide with diazonium salts resulted in the formation of the corresponding thiophene derivatives 4a–c. Additionally, the reaction of acetoacetamide derivative 3 with malononitrile, ethyl cyanoacetate, or 2-cyanoacetamide, along with elemental sulfur, under refluxing in dioxane containing triethylamine afforded thiophene-containing derivatives 5a–c. Furthermore, compound 3 reacted with phenyl isothiocyanate in dry dimethylformamide and K₂CO₃ to yield compound 7. In situ alkylation of the non-isolable salt 6 was achieved by the addition of methyl iodide, resulting in the formation of methylthio-thiophene-2-carboxamide 8. Compound 7 was employed with numerous alpha-halogenated reagents in ethanol, affording thiazole derivative 9 and thiophene derivatives 10a and 10b, respectively. Moreover, compound 8 was reacted with hydrazine to produce the 1H-pyrazole-4-carboxamide derivative 11. Additionally, refluxing acetoacetamide derivative 3 with malononitrile and/or ethyl cyanoacetate in dioxane, in the presence of catalytic amount of triethylamine afforded 4-imino-3,7-dimethyl-4H-pyrido[1,2-a]thieno[3,2-e]pyrimidin-9(5H)-one derivatives 12a and 12b. Furthermore, the reactivity of acetoacetamide derivative 3 with 2-cyanoacetohydrazide was investigated through refluxing the reactants in dioxane, which subsequently yielded the corresponding cyanoacetamide derivative 13. The chemical identity of the newly synthesized compounds was determined by employing infrared spectroscopy (IR), ¹H NMR, and ¹³C NMR techniques. Newly synthesized heterocycles incorporating thiophenes were evaluated for their antioxidant and antimicrobial potentials. Notably, thiophene scaffolds 5a, 10b, 11, and 13 displayed notable antioxidant and antimicrobial activities.