Journal of Heterocyclic Chemistry最新文献

Investigation of the microwave-assisted condensation of anthranilic acid derivatives with ethylpiperidine isothiocyanates into 2-thioxoquinazolin-4-ones revealed an intramolecular cyclization into 2,3-dihydro-5H-thiazolo[2,3-b]quinazolinones. The study of reaction parameters demonstrated that temperature is a key factor controlling this transformation, while anthranilic acid substituents further modulate the reaction outcome. Here we report the promotion of the intramolecular cyclization to thiazoloquinazoline at high temperatures (200°C), whereas lower temperature (125°C) selectively favors the formation of 2-thioxoquinazolin-4-one in good yield. These findings provide refined conditions for the synthesis of 2-thioxoquinazolin-4-one derivatives and expand the way to synthesize 2,3-dihydro-5H-thiazolo[2,3-b]quinazolinone derivatives of potential medicinal interest.

For the first time, the multicomponent reaction of labile 2-aminothiophenes with aldehydes and malononitrile was investigated. We have shown that the considered process leads to the formation of thieno[2,3-b]pyridine derivatives containing cyano- and amino groups. Sodium salts of 2-aminothiophene-3-carboxylic acids were utilized as straightforward precursors for the generation of unstable 2-aminothiophenes in situ. Based on the presented multicomponent condensation, the general method for the synthesis of final 6-aminothieno[2,3-b]pyridine-5-carbonitriles was designed. The elaborated procedure allowed us to obtain a large array of target products with yields up to 68%. Advantages of the developed approach are easily available starting materials, atom economy, and convenient isolation of prepared compounds without chromatographic purification. The structure of one representative of the synthesized thieno[2,3-b]pyridines was confirmed by X-ray analysis.

A new strategy is described for the first time to synthesize a heterocyclic hybrid system of 1,5-disubstituted-1H-tetrazole-bis-1,2,3-triazoles through a double one-pot sequence. The approach involves (i) a one-pot five-component process to obtain the key 1,5-DS-T-bis-propargyl compounds 11a–n, using propargylamine as an orthogonal reagent, followed by (ii) a pseudo-three-component reaction consisting of a double CuAAC process with aromatic azides to afford the target hybrids 6a–n in moderate yields. The protocol is operationally simple, proceeds under mild reaction conditions, and some products were purified by recrystallization from methanol. Notably, this is the first example of a higher-order multicomponent sequence combined with a classical pseudo-multicomponent reaction, underscoring the synthetic utility of this approach for the rapid assembly of structurally complex hybrid scaffolds relevant to medicinal chemistry. Finally, the feasibility of accessing the target hybrids in a truly one-pot manner was demonstrated starting from propargylamine, with the overall process forming six C–N bonds, one C–C bond, and one N–N bond within a single operation.

A novel three-series of selenium-containing heterocycles (SeCHet) incorporating tertiary amine functionalities, namely N-alkyl selenopyridines (5a–e and 6a–c) and N-alkyl selenopheno[2,3-b]pyridines 7a–d, were successfully synthesized through the reaction of selenium-chloroacetamide scaffold derivatives 3a and 3b with various secondary amines. These compounds were designed based on the well-established biological importance of both selenium-based heterocyclic compounds and amine-containing molecules in biological activities, particularly their antioxidant and antibacterial properties against selected Gram-positive and Gram-negative bacterial strains. Several compounds exhibited promising biological activity, with derivatives containing the diethylamino and piperidine moieties showing enhanced antibacterial effects, particularly against Bacillus cereus , with an inhibition percentage more than the standard drug (ciprofloxacin). In addition, notable antioxidant activity was observed for selected compounds; the activity of compound 5b was comparable to vitamin C, with an inhibition percentage similar to vitamin C, 74%. Derivatives 6a and 7a showed the highest antioxidant performance, with inhibition rates of 72% and 67%, respectively, indicating the potential of these structures as biologically active agents. Overall, the obtained results highlight the significance of incorporating tertiary amine and selenopyridine functionalities in the development of new compounds with potential pharmaceutical applications.

Thiazine and oxazine derivatives are important heterocyclic structural motifs that confer biological activity. These compounds have extensive applications in a variety of fields, including medicine, materials science, agriculture, and organic chemistry. This review provides a comprehensive analysis of current trends in the synthesis of thiazines and oxazines, as well as their isomeric forms via α,β-enal transformations. The structural features of the substrates, their influence on the selectivity and yields of the target products, reaction conditions, types of catalysts, transformation mechanisms, and prospects for the application of the obtained heterocycles are discussed in detail. Works published since 2015 are highlighted, and earlier sources are referenced as needed.

The rise of drug or multidrug resistance in Plasmodia strains has made malaria the most important tropical parasitic disease. To address this issue, new antimalarial drugs must be developed. As a fundamental building block in organic synthesis, materials science, and pharmaceutical chemistry, the triazole scaffold is an essential part of heterocyclic chemistry. Because of their broad chemical properties and potential biological applications, including antimalarial, the synthesis of triazoles has gained significant attention in the field of organic chemistry. This review primarily focuses on the synthesis, the wide range of antimalarial activities of several hybridized 1,2,3-triazoles and 1,2,4-triazoles, and the structure–activity relationships (SAR) reported since 2022, which target various stages of the Plasmodium life cycle. Because of their adaptability, they are extremely efficient against both drug-sensitive and drug-resistant strains of P. falciparum , making them indispensable resources in areas where resistance is common. Even higher antimalarial effectiveness has been achieved by the synergistic effects of mixing the triazole moiety with additional pharmacophores. This strategy may be able to surpass current resistance mechanisms and offer a more long-lasting way to treat malaria. Triazole hybrid compounds continue to play a significant role in malarial chemotherapy despite the development of numerous antimalarial leads. Researchers can further investigate and innovate in the synthesis, antimalarial evaluation, and structure–activity relationship (SAR) studies of triazoles as pharmaceuticals by including them as crucial components in drug discovery, thereby examining their potential therapeutic importance.

In the present communication a novel method for the synthesis of thieno[2,3-b]pyrrole derivatives was developed. The considered approach is based on a previously undescribed recyclization of thieno[2,3-b]pyridin-6(5H)-ones bearing aroyl fragment under the action of p-toluenesulfonic acid in alcoholic media. The elaborated general protocol allowed us to obtain a set of 22 target esters of (thieno[2,3-b]pyrrol-4-yl)acetic acids with yields up to 84%. Readily accessible starting materials, mild reaction conditions, atom economy, and convenient isolation of the final products without chromatographic purification are the advantages of the presented procedure. The structure of one of the prepared thieno[2,3-b]pyrroles was proved by X-ray diffraction.

The photochemical behavior of terarylenes bearing allomaltol and 2-aminooxazole fragments has been investigated, providing the basis for an efficient strategy toward substituted cyclopenta[b]quinoxalines. Upon irradiation of starting compounds with 400 nm visible light, the allomaltol moiety undergoes selectively ESIPT-induced contraction of the pyranone ring, affording highly reactive α-hydroxycyclopentene-1,2-dione intermediates, as evidenced by ¹H NMR monitoring. Notably, the free amino group does not inhibit the photorearrangement, in contrast to related amino-substituted terarylenes. In situ trapping with 1,2-phenylenediamines affords cyclopenta[b]quinoxaline derivatives in yields of up to 87%, while phenylhydrazine gives separable E/Z hydrazones. The one-pot protocol proceeds under mild, metal- and base-free conditions.

Electrocatalytic cycloadditions of π-systems have emerged as versatile and sustainable strategies for constructing structurally diverse carbocycles and heterocycles. By harnessing anodic oxidation or cathodic reduction, these transformations replace stoichiometric chemical oxidants and metal catalysts with electricity as a traceless reagent, enabling environmentally benign, redox-neutral, and atom-economical pathways. Cycloadditions such as [2 + 1], [2 + 2], [2 + 2 + 2], [3 + 2], [4 + 2], and [5 + 2] efficiently generate cyclobutanes, cyclopentanes, cyclohexanes, and fused polycycles, often proceeding via radical-cationic, 1,3-dipolar, or stepwise electron-transfer mechanisms. Mechanistic studies highlight the critical roles of radical stabilization, electrochemical potential, and substrate polarity in dictating chemo-, regio-, and stereoselectivity. Recent advances include multicomponent, cascade, flow-electrochemical, and asymmetric approaches that expand structural complexity while minimizing waste. Collectively, these studies underscore the versatility of electrocatalytic cycloadditions as a green, tunable, and scalable platform for the synthesis of complex carbocyclic and heterocyclic architectures. This review positions π-system electrocatalysis as a unifying and sustainable paradigm for constructing molecules of relevance to pharmaceuticals, agrochemicals, and materials science, highlighting its potential to replace traditional oxidants and metal-based protocols in modern synthetic chemistry.

In the present work, we describe the first example of constructing the 3-hydroxypyridin-2(1H)-one core based on the interaction of heterocyclic enamines with ethyl bromopyruvate. Utilizing a wide range of substituted 5-aminopyrazoles as an enamine component we have shown that the considered condensation leads to the formation of pyrazolo[3,4-b]pyridin-6-one derivatives containing a hydroxyl group. Relying on the investigated reaction a general approach to the synthesis of the target bicyclic system was developed. The application of elaborated protocol to a set of diverse 5-aminopyrazoles allowed us to obtain an array of 5-hydroxy-1,7-dihydro-6H-pyrazolo[3,4-b]pyridin-6-ones with yields up to 82%. The undoubted advantages of the presented method are easily available starting materials, atom economy and facile isolation of the final products without chromatographic purification. The structure of the prepared compounds was confirmed employing ¹H and ¹³C NMR spectroscopy, high-resolution mass spectrometry as well as data of X-ray analysis.