Synthetic Communications最新文献

{"title":"Benzethonium chloride:glycerol (1:2) deep eutectic solvent promoted green synthesis of benzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylate and evaluation of its anti-diabetic activity","authors":"Vimal Dinesh Vishwa (Data curation Formal analysis Investigation Methodology Validation),&nbsp;Peeli Kumar Anjali (Data curation Formal analysis),&nbsp;Dhamodharan Swathi (Data curation Formal analysis),&nbsp;Muniyan Ramasamy Kuppusamy (Formal analysis Validation Writing – original draft Writing – review & editing),&nbsp;Devendiran Parthiban (Conceptualization Methodology Project administration Resources Supervision Validation Writing – original draft Writing – review & editing)","doi":"10.1080/00397911.2026.2725167","DOIUrl":"10.1080/00397911.2026.2725167","url":null,"abstract":"<div><div>In this study, we present the preparation of benzethonium chloride:glycerol (1:2) deep eutectic solvent (DES) by mixing benzethonium chloride and glycerol in a 1:2 ratio and heating at 80 °C for approximately 30 min. The prepared BztCl:Gly DES was utilized as an eco-friendly reaction medium and an eco-benign catalyst for the one-pot multicomponent synthesis of ethyl 2-methyl-4-aryl-1,4-dihydrobenzo[4,5]imidazo[1,2-<em>a</em>]pyrimidine-3-carboxylate derivatives via the cyclocondensation of equimolar amounts (5 mmol each) of aromatic aldehydes, ethyl acetoacetate, and 2-aminobenzimidazole at 110 °C. The reaction proceeded rapidly, affording 11 distinct benzo[4,5]imidazo[1,2-<em>a</em>]pyrimidine derivatives in excellent yields ranging from 77% to 93% within 45–90 min. The products were isolated by filtration, purified via recrystallization, and structurally confirmed using infrared spectroscopy (IR), proton and carbon nuclear magnetic resonance spectroscopy (¹H and 1³C NMR), and electrospray ionization mass spectrometry (ESI-MS). BztCl:Gly DES was recovered by water addition, which precipitated the organic products. The aqueous phase was then evaporated under reduced pressure, enabling efficient reclamation and reuse BztCl:Gly DES. Remarkably, BztCl:Gly DES demonstrated excellent stability and sustained catalytic activity, maintaining its efficiency across five consecutive reaction cycles. The α-amylase inhibitory activity of the synthesized samples was evaluated across a concentration range of 25 to 500 μg/mL. All samples exhibited a clear dose-dependent inhibitory effect of IC₅₀ value ranging 25–44 μg/mL, where the percentage of inhibition increased progressively with rising concentrations. Thus, BztCl:Gly DES acts as an efficient catalyst and reaction medium for this organic transformation by enables hydrogen bonding and nucleophilic activation, promoting imine formation and cyclization, collectively accelerating the reaction and improving product yield. This study presents the first use of a biocompatible, recyclable benzethonium chloride-based deep eutectic solvent (DES) as both a highly efficient catalyst and reaction medium for the synthesis of benzo[4,5]imidazo[1,2-<em>a</em>]pyrimidine derivatives. Compared to traditional volatile organic solvent methods, this approach achieves excellent yields under mild conditions while offering promising <em>in vitro</em> α-glucosidase inhibitory activity.</div></div>","PeriodicalId":22119,"journal":{"name":"Synthetic Communications","volume":"56 16","pages":"Pages 1250-1273"},"PeriodicalIF":2.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148981063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular hybridization strategy for the design of benzimidazolyl-retrochalcone derivatives as antifungal agents: Synthesis, characterization, and CYP51-based computational evaluation","authors":"Koné Aboudramane (Investigation Methodology Validation),&nbsp;Souleymane Coulibaly (Conceptualization Methodology Validation Writing – original draft),&nbsp;Nanan Landry Frejus (Data curation Formal analysis Investigation Writing – original draft),&nbsp;Chany Anne-Caroline (Data curation Formal analysis),&nbsp;Collet Sylvain (Data curation Investigation Supervision Validation),&nbsp;Sissouma Drissa (Conceptualization Supervision Validation)","doi":"10.1080/00397911.2026.2725883","DOIUrl":"10.1080/00397911.2026.2725883","url":null,"abstract":"<div><div>The growing resistance of <em>Candida</em> species highlights the need for antifungal agents targeting validated fungal enzymes. In this study, a series of benzimidazole-based retrochalcone derivatives was designed, and evaluated as potential inhibitors of lanosterol 14α-demethylase (CYP51). The design strategy combined benzimidazole with a retrochalcone scaffold to improve the predicted binding within the CYP51 active site. The compounds were tested <em>in vitro</em> against <em>Candida species</em> using a microdilution assay. Several derivatives showed significant, strain-dependent activity compared to ketoconazole. Compounds <strong>4c</strong>, <strong>4h</strong> exhibited outstanding potency against <em>C. glabrata</em> (up to 71-fold improvement), while compound <strong>4e</strong> showed remarkable activity against <em>C. albicans</em>. Compounds <strong>4g</strong> and <strong>4i</strong> displayed balanced activity across multiple strains. Molecular docking provided a computational rationale for the observed antifungal activity. Enhanced activity was linked to improved hydrogen bonding, hydrophobic interactions, aromatic stacking, and, in some cases, interactions with heme cofactor. Overall, these results identify benzimidazole–retrochalcone hybrids as promising antifungal scaffolds.</div></div>","PeriodicalId":22119,"journal":{"name":"Synthetic Communications","volume":"56 16","pages":"Pages 1274-1292"},"PeriodicalIF":2.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148981064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PS-BEMP-catalyzed solvent-free Knoevenagel condensation under microwave activation: Extension to weakly acidic β-sulfuramides","authors":"Lamia Saidi (Data curation Formal analysis Investigation),&nbsp;Aouicha Benmaati (Formal analysis Validation Writing – original draft),&nbsp;Riad Mustapha Kerbadou (Formal analysis Investigation),&nbsp;Abdelatif Bouyacoub (Validation),&nbsp;Thierry Constantieux (Methodology Visualization Writing – review & editing),&nbsp;Hadjira Habib Zahmani (Conceptualization Investigation Methodology Visualization Writing – original draft Writing – review & editing)","doi":"10.1080/00397911.2026.2724294","DOIUrl":"10.1080/00397911.2026.2724294","url":null,"abstract":"<div><div>The Knoevenagel condensation is a fundamental transformation for carbon–carbon bond formation. Herein, we report a polystyrene-supported 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine (PS-BEMP)-catalyzed, solvent-free Knoevenagel protocol conducted at room temperature for highly activated substrates and under microwave-assisted conditions for less reactive active methylene compounds. Aromatic and heteroaromatic aldehydes reacted with a range of active methylene partners to afford the corresponding α,β-unsaturated products in isolated yields of up to 98% within 4–15 min. Most products were isolated after catalyst filtration and solvent evaporation without column chromatography. The protocol was further extended to weakly acidic β-sulfuramides (pKₐ ≈ 23), providing sulfur-containing vinyl derivatives in isolated yields of 21–90%, including several previously unreported compounds. PS-BEMP was recovered and reused over five cycles with only a moderate decrease in catalytic performance. However, no conversion was observed with selected highly stabilized 1,3-dicarbonyl substrates, including diethyl malonate, ethyl and tert-butyl acetoacetates, and 2,4-pentanedione, thereby defining a limitation of the methodology.</div></div>","PeriodicalId":22119,"journal":{"name":"Synthetic Communications","volume":"56 16","pages":"Pages 1293-1312"},"PeriodicalIF":2.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148981050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper(II)/TBHP-mediated oxidation of isoindolinones and other substrates—effect of air and oxygen","authors":"Shramana Ghosh (Investigation),&nbsp;Frederick A. Luzzio (Conceptualization)","doi":"10.1080/00397911.2026.2724297","DOIUrl":"10.1080/00397911.2026.2724297","url":null,"abstract":"<div><div>When employed in conjunction with <em>tert</em>-butyl hydroperoxide (TBHP), iron(III) and copper(II)-catalyzed oxidation systems have proven to be effective in transforming isoindolinones to the corresponding phthalimides. Considering both metal-mediated processes, one of the issues that still requires attention is the extended reaction times required for isoindolinones to give modest to good yields of imide in the presence of sensitive functionality. As an extension of our previously reported Cu(II)/TBHP protocol, a plausible avenue to enhance the copper-catalyzed process was to conduct the Cu(II)/TBHP-mediated oxidations in the presence of molecular oxygen or air. Consequently, improvement in reaction time and/or isolated yield with selected substrates was observed with Cu(II)/TBHP and oxygen at atmospheric pressure, while at the same time side reactions leading to unwanted by-products from over-oxidation were not evident. The Cu(II)/TBHP system was also applied to selected non-nitrogenous benzylic substrates to examine the broader utility of the oxidation conditions.</div></div>","PeriodicalId":22119,"journal":{"name":"Synthetic Communications","volume":"56 16","pages":"Pages 1313-1323"},"PeriodicalIF":2.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148981051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper-catalyzed synthesis of heterocycles via single and two-electron pathways","authors":"Trapti Porwal (Data curation Writing – original draft),&nbsp;Rajnish Kumar (Conceptualization Supervision Writing – original draft Writing – review & editing),&nbsp;Shrishti Tripathi (Data curation),&nbsp;Salahuddin (Supervision)","doi":"10.1080/00397911.2026.2682562","DOIUrl":"10.1080/00397911.2026.2682562","url":null,"abstract":"<div><div>Heterocyclic compounds serve as indispensable frameworks in pharmaceuticals, agrochemicals, and advanced materials, yet achieving their efficient and sustainable synthesis continues to pose a central challenge in modern organic chemistry. Copper, owing to its natural abundance, low toxicity, and unique ability to access multiple oxidation states (Cu(0), Cu(I), Cu(II), and Cu(III)), has emerged as a powerful and sustainable alternative to precious-metal catalysts for constructing these architectures. This review comprehensively surveys copper-catalyzed heterocycle synthesis published between 2015 and 2024, with particular emphasis on mechanistic diversity, including single-electron transfer and two-electron pathways, such as oxidative addition and reductive elimination. We systematically examine how copper-mediated C–H functionalization, multicomponent reactions, cycloisomerizations, and click chemistry enable the assembly of nitrogen-, oxygen-, and sulfur-containing heterocycles—including pyrroles, furans, thiophenes, indoles, benzimidazoles, benzofurans, and triazoles—under mild conditions, frequently without ligands or solvents. Key advances in microwave-assisted and flow-chemistry protocols that align with green chemistry principles are highlighted. Mechanistic rationale and structure–reactivity relationships are discussed to aid catalyst design. The review further identifies current challenges, proposes strategies to address them, and outlines future directions, including integration with photoredox and electrochemical techniques, to underscore the industrial relevance and scalability of copper-catalyzed heterocyclic synthesis.</div></div>","PeriodicalId":22119,"journal":{"name":"Synthetic Communications","volume":"56 16","pages":"Pages 1215-1249"},"PeriodicalIF":2.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148981062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of thioamides from nitriles in 1,4-dioxane by using CH3SO3H and thioacetamide","authors":"Xiaoyun Ma (Methodology Validation Writing – original draft Writing – review & editing),&nbsp;Shurui Wang (Validation),&nbsp;Dayan Luo (Methodology),&nbsp;Jun Zhao (Validation)","doi":"10.1080/00397911.2026.2710157","DOIUrl":"10.1080/00397911.2026.2710157","url":null,"abstract":"<div><div>A method for the preparation of thioamides from nitriles using CH₃SO₃H and thioacetamide is described. Using this method, nitriles including aromatic nitriles, aromatic heterocyclic nitrile and aliphatic nitriles were converted into the corresponding thioamides in moderate to good yields. The reaction proceeded smoothly at reflux temperature in 1,4-dioxane, with reaction times ranging from 8 to 12 hours. Functional groups including halogen, nitro, alkoxy, hydroxy, ester, and acyl remained unaltered, indicating good chemoselectivity. Thioacetamide reacts with nitriles in the presence of CH₃SO₃H to yield acetonitrile, as deduced from experimental evidence.</div></div>","PeriodicalId":22119,"journal":{"name":"Synthetic Communications","volume":"56 15","pages":"Pages 1178-1185"},"PeriodicalIF":2.0,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148940255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyanobenzaldehydes as key synthons for the construction of fused heterocyclic scaffolds: a mini-review","authors":"Rozita Yazzaf (Writing – original draft),&nbsp;Hossein Kianfard (Writing – review & editing),&nbsp;Mohammad Mahdavi (Supervision)","doi":"10.1080/00397911.2026.2680555","DOIUrl":"10.1080/00397911.2026.2680555","url":null,"abstract":"<div><div>Cyanobenzaldehydes have emerged as highly valuable and versatile synthons in heterocyclic chemistry owing to the unique coexistence of electrophilic aldehyde and nucleophilic nitrile functionalities within a single molecular framework. This dual reactivity enables diverse annulation and cyclization strategies, providing efficient access to a wide range of fused heterocyclic scaffolds. This mini-review summarizes recent advances in the synthetic applications of 2-cyanobenzaldehydes for the construction of fused heterocycles, with an emphasis on product-oriented classification. The reported heterocyclic skeletons are systematically categorized into five major groups: isoindoline derivatives, isobenzofuran derivatives, isoquinoline derivatives, indole and benzimidazole derivatives, and pyrrolopyrimidine derivatives. Representative synthetic methodologies, key reaction conditions, and mechanistic aspects are discussed to highlight the structural diversity and synthetic potential enabled by 2-cyanobenzaldehydes. This focused overview aims to provide a concise and organized resource for researchers interested in the design and synthesis of fused heterocyclic frameworks using 2-cyanobenzaldehyde-based building blocks.</div></div>","PeriodicalId":22119,"journal":{"name":"Synthetic Communications","volume":"56 15","pages":"Pages 1145-1177"},"PeriodicalIF":2.0,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148940256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A concise route to a racemic elacestrant intermediate via Ni-catalyzed reductive coupling","authors":"Keyang Zhang (Data curation Formal analysis Investigation),&nbsp;Deli Sun (Data curation Writing – review & editing),&nbsp;Hegui Gong (Conceptualization Supervision Writing – original draft)","doi":"10.1080/00397911.2026.2716093","DOIUrl":"10.1080/00397911.2026.2716093","url":null,"abstract":"<div><div>Elacestrant is an FDA-approved drug for breast cancer. In this work, we present a synthetic strategy of a key intermediate (compound <strong>24</strong>) of racemic elacestrant building upon nickel-catalyzed cross-electrophile coupling (XEC) of 2-bromoanilines and 2-bromotetrahydronaphthalene. The method highlights excellent tolerance of aryl bromides bearing free amines, which effectively coupled with a wide range of alkyl bromides featuring aryl-fused rings and open-chains. The method merits easily accessible starting materials, cost-effective nickel catalyst, mild reaction conditions, and easy-to-handle operation.</div></div>","PeriodicalId":22119,"journal":{"name":"Synthetic Communications","volume":"56 15","pages":"Pages 1196-1204"},"PeriodicalIF":2.0,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148940257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photoaccelerated aza-Michael addition of pyrazoles to α, β-unsaturated carbonyl compounds","authors":"Yanhui Zhao (Data curation Methodology Validation Writing – original draft Writing – review & editing),&nbsp;Xue Zhang (Conceptualization Funding acquisition Methodology Project administration Writing – original draft Writing – review & editing),&nbsp;Mingzhao Li (Data curation Formal analysis Investigation Methodology Writing – original draft),&nbsp;Jiaman Li (Data curation Formal analysis Methodology Writing – original draft),&nbsp;Xinxin Liu (Data curation Formal analysis Investigation Writing – original draft),&nbsp;Haifeng Yu (Conceptualization Funding acquisition Writing – original draft Writing – review & editing)","doi":"10.1080/00397911.2026.2711086","DOIUrl":"10.1080/00397911.2026.2711086","url":null,"abstract":"<div><div><em>N</em>-Alkylpyrazoles are an important subclass of pyrazoles due to their good physiological and pharmacological activities. Here, we report photoaccelerated aza-Michael addition of pyrazoles to α, β-unsaturated carbonyl compounds to provide <em>N</em>-alkylpyrazoles. The advantages, including mild conditions, broad scope, ease of scale-up, high atom-economy, avoiding the use of metals, bases, photocatalysts and additives, make the reaction useful and practical.</div></div>","PeriodicalId":22119,"journal":{"name":"Synthetic Communications","volume":"56 15","pages":"Pages 1186-1195"},"PeriodicalIF":2.0,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148940258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Convenient synthesis of anhydrides from carboxylic acids by Mitsunobu reaction under mild conditions","authors":"Yu-Qiang Zhou (Conceptualization Methodology Resources Supervision Writing – original draft),&nbsp;Li-Li Jiang (Data curation Formal analysis Investigation Writing – original draft),&nbsp;Feier Ren (Data curation Investigation Writing – original draft Writing – review & editing),&nbsp;Yu Zhang (Data curation Formal analysis Investigation),&nbsp;Ronglin Lu (Data curation Investigation),&nbsp;Mengyu Cheng (Investigation Validation),&nbsp;Wei-Hao Rao (Funding acquisition Supervision Writing – review & editing)","doi":"10.1080/00397911.2026.2720919","DOIUrl":"10.1080/00397911.2026.2720919","url":null,"abstract":"<div><div>Anhydrides serve not only as highly effective acylating agents but also as pivotal intermediates in organic synthesis, and are therefore widely employed in the construction of polymers, pharmaceuticals, and other commodity chemicals. Despite the availability of various synthetic strategies, existing methods are often hampered by the use of unstable or difficult-to-handle reagents, laborious workup procedures, and a substrate scope largely restricted to symmetrical derivatives. We herein report a convenient and efficient one-step method to anhydrides from carboxylic acids via the Mitsunobu reaction. The protocol accommodates a broad range of both aromatic and aliphatic carboxylic acids under mild and neutral conditions, affording the corresponding symmetrical and unsymmetrical anhydrides in satisfactory yields. This approach addresses key limitations of existing methodologies, offering a practical and versatile alternative for anhydride synthesis.</div></div>","PeriodicalId":22119,"journal":{"name":"Synthetic Communications","volume":"56 15","pages":"Pages 1205-1214"},"PeriodicalIF":2.0,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148940259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}