Pentafluorophenyl iodine(III) diacetate (F5-PIDA) is an electron-deficient hypervalent iodine(III) reagent with growing utility in modern synthetic methodology, including iodine(III)-mediated ring-expansion chemistry. However, its application as a stoichiometric reagent requires reliable access to preparative amounts. This article describes a practical chromatography-free protocol for the preparation of F5-PIDA on a ca. 300 g scale by the oxidation of pentafluoroiodobenzene with sodium hypochlorite pentahydrate in acetic acid. The product was isolated by a simple slurry trituration in the hexane/MTBE mixture giving F5-PIDA in the yield of 65% and the purity of ≥ 98%. The thermogravimetry-differential thermal analysis has shown that F5-PIDA is stable up to approximately 100-110 °C, while the rapid decomposition occurs above this temperature range. The protocol developed provides a reliable preparative access to high-purity F5-PIDA and practical thermal data for its safe use.
Hierarchical titanosilicate zeolites of the MFI structural type (zeolites with the MFI framework topology according to the classification of the International Zeolite Association) showed a high catalytic activity in the synthesis of cyclic carbonate from styrene in the presence of tert-butyl hydroperoxide as an oxidant. It has been shown that the combination of the redox properties of titanium centers with the acid-base characteristics of the zeolite matrix ensures the efficient implementation of the tandem process within a single reaction medium. The results obtained confirm the potential of titanium-containing zeolites as an effective platform for creating heterogeneous catalysts for the direct conversion of olefins into cyclic carbonates.
Cyclic voltammetry was applied to a series of substituted bis(2-nitrophenyl)disulfides in acetonitrile containing tetraethylammonium tetrafluoroborate under unified experimental conditions. Seven compounds were initially considered (S01-S07). One of them (S07) proved practically insoluble in acetonitrile and was excluded from further analysis. As a result, the electrochemical study was performed for six compounds (S01–S06). Among them, three compounds had voltammograms suitable for semiquantitative treatment, including the comparison of cathodic peak currents, whereas the remaining three compounds provided only qualitative electrochemical information due to their limited solubility and attenuated current response. The multistage cathodic behavior was observed in all cases suitable for analysis. The comparison with nitrobenzene measured under identical conditions indicated a nitro-related reduction process in the region of approximately –1.1 V vs Ag/AgCl and a stronger cathodic process near –1.7 V, which was consistent with the cleavage of the disulfide bond and might overlap with a deeper nitro-related reduction. Substituent effects were evident both in peak potentials and, for the more soluble subset, in the cathodic current value. The results show that cyclic voltammetry is a useful screening tool for substituted aromatic nitrodisulfides, even when the solubility prevents the uniform quantitative comparison across the whole series.
Imidazo[1,5-a]pyridine carboxylic acids are useful building blocks for medical chemistry, but their synthesis scale-up and isolation depend strongly on pH. For zwitterion-prone representatives, a direct titration of acids does not always reveal the basicity of the heteroaromatic center, which is critical for their further use. Therefore, a series of acids, their corresponding esters, and hydrochlorides were analyzed by the potentiometric titration together with 1H/13C NMR, HPLC, LCMS, and HRMS. The acids showed apparent pKa values of 5.13-6.11, while the esters exposed the basic-center pKa values in the range of 2.75-4.64. NMR data indicate close electronic similarity within the acid/ester pairs, supporting the use of esters as models for acids with masked basicity.
Chondroitin sodium sulfate is an anionic polysaccharide widely used in pharmaceutical practice as an active ingredient of mono- and multicomponent medicinal products, and its quantitative determination is an essential stage of the quality control. It has been found that the application of potentiometric titration with ion-selective electrodes can increase the accuracy and objectivity of the quantitative analysis, which is of great importance for ensuring the quality and safety of medicines. The aim of the study was to develop and validate a potentiometric method for the quantitative determination of chondroitin sodium sulfate in the substance and in a combined medicinal product in the form of the sachet powder. The study objects were chondroitin sodium sulfate substance and a combined medicinal product containing chondroitin sodium sulfate in combination with D-glucosamine sodium sulfate, methylsulfonylmethane, sodium hyaluronate, ascorbic and citric acids, and sorbitol. The conditions of the potentiometric titration with 0.001 M solution of cetylpyridinium chloride were studied using an ion-selective electrode based on cetylpyridinium ionic associates with some lipophilic anions. The titrant was standardized using sodium dodecyl sulfate as a primary standard, as well as the substance itself. The equivalence point was determined from the titration curve and its mathematically processed forms (differential curve, first derivative, and Gran functions). It has been found that the plasticized membrane ion-selective electrodes based on cetylpyridinium associates with dodecyl sulfate and tetraphenylborate anions are characterized by a stable near-Nernstian response in the operating range of cetylpyridinium concentrations of 10-3-10-6 mol L-1. The analytical characteristics of the electrodes remained stable for at least 30 consecutive titrations. The selectivity of the reaction between chondroitin sodium sulfate and cetylpyridinium chloride was found, ensuring a clear determination of the equivalence point even in the presence of other mixture components. The influence of pH on the titration results was evaluated; it was shown that in the pH range of 4-8 the shape of titration curves and potential values remained constant, confirming the robustness of the method. The accuracy, precision, linearity (within 80–120% of the nominal content of the analyte), and the reproducibility of the method were characterized. It has been experimentally demonstrated that the potentiometric method proposed is accurate, selective, and reproducible for the quantitative determination of chondroitin sodium sulfate both in pure form and in combined medicinal products. The results obtained confirm the analytical suitability of the method developed and the prospects of its implementation in the pharmaceutical analysis practice for the quality control of substances and combined medicinal products of small-scale and industrial production.
Di-, tetra-, and hexamethine merocyanine dyes bearing donor heterocyclic end groups of different electron-donating abilities and the 9H-fluorene-2,7-dicarbonitrile moiety as the acceptor end group have been synthesized. Their UV/Vis absorption spectra have been studied in solvents of varying polarity, and their electronic nature and vertical transitions have been investigated via (TD)-DFT calculations. The results indicate that the electronic structure of these merocyanines approaches the neutral polyene limit, becoming increasingly polyene-like in low-polarity solvents and upon increasing the polymethine chain length, which indicates the weak electron-acceptor ability of the 9H-fluorene-2,7-dicarbonitrile moiety. Nevertheless, longer vinylogs, especially those containing the 4H-pyran donor end group, exhibit the inverse solvatochromic behavior, which is highly unusual for such weakly dipolar merocyanines. A possible explanation for this effect has been proposed although its rigorous verification would require higher-level quantum-chemical calculations with solvent effects taken into account.
An optimized biocatalytic oxidation protocol has been developed for the efficient conversion of benzylic and allylic alcohols into their corresponding aldehydes. The sustainable method uses lyophilized mycelia of Bjerkandera adusta white-rot fungus as a catalyst in the aqueous medium with 2-propanol (10% v/v) as a co-solvent, and operates under mild conditions to give high yields for a wide range of substrates. On a preparative scale, the approach allowed the synthesis of important aldehydes, including benzaldehyde, piperonal, cinnamaldehyde, cuminaldehyde, methoxybenzaldehydes, and citral.
Three thiazolo[3,2-b][1,2,4]triazol-7-ium hexabromotellurates 1-3 were synthesized via the electrophilic heterocyclization of methallyl thioether precursors using a classical tellurium(IV) electrophilic reagent generated in situ from TeO2 and 1 M hydrobromic acid. The resulting salts were comprehensively screened for the antimicrobial activity against five clinically relevant pathogens: Staphylococcus aureus, Candida albicans, Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa. Biological assays revealed that compound 1 containing a 2-(4-pyridyl) substituent demonstrated the strongest activity profile, particularly against C. albicans (MIC = 15.625 μg mL-1) and E. coli (MIC = 31.25 μg mL-1). Compound 2, substituted with the 3-hydroxyphenyl moiety, also showed a significant antifungal efficacy, while compound 3 (with the 2-phenyl substituent) exhibited a relatively low activity. To rationalize these differences, the molecular docking was performed targeting MurB (UDP-N-acetylenolpyruvoylglucosamine reductase, PDB 1MBT) and DNA gyrase B (GyrB, PDB 4URO), two bacterial enzymes known to be essential for the viability of Gram-negative pathogens. The docking results confirmed the experimental data, showing strong π–π stacking and hydrogen bonding between compound 1 and the FAD-containing binding pocket of MurB. This work highlights the utility of the tellurium-induced annulation in producing biologically potent heterocycles and emphasizes the structure–activity relationships driven by substituents in position 2 of the fused scaffold.
The complexation of tetrahydroxycalix[4]arene-methyldimethylphosphine oxide (CMPO), tetrahydroxythiacalix[4]arene-methyldimethylphosphine oxide (TCMPO), and tetrapropoxycalix[4]arene-methyldiethylphosphine oxide (CEPO) with active pharmaceutical ingredients of antiviral drugs Remdesivir, Nevirapine, Vesatolimod, Bictegravir, Emtricitabine, and Tenofovir in the water medium was studied using the RP HPLC method. By analyzing the dependence of the drug capacity values on the concentration of calixarenes in the chromatographic mobile phase, the stability constants (KA = 1100 - 12000 M-1) of the complexes formed were determined. Quantum-chemical calculations show that the antiviral drugs form supramolecular exo-complexes with the calixarene-phosphine oxide molecules. These complexes can be stabilized by intermolecular hydrogen bonds between the proton acceptor P=O groups and the proton donor groups of antiviral drugs.
A practical and scalable cyclization method for the preparation of C4-functionalized isoxazolidine and pyrazolidine building blocks is described. The methodology is based on the use of commercially available 1,3-dihalide and protected hydroxylamine or hydrazine derivatives under unified NaH/DMF conditions, enabling direct assembly of both N,O- and N,N-heterocycles. The process is operationally robust and successfully implemented on an over 100 g scale. The oxidative conversion of exocyclic alkene intermediates made it possible to obtain isoxazolidin-4-one and pyrazolidin-4-one scaffolds. The resulting pyrazolidine derivatives demonstrate a broad tolerance to reductive and oxidative conditions, whereas isoxazolidines exhibit certain stability limitations. The combination of the modular C4 diversification, orthogonal nitrogen protection, and preparative scalability transforms these saturated heterocycles into practically accessible building blocks for medicinal chemistry applications.
In this study, an optimized method for the synthesis of azaindoles was developed and successfully scaled up to a 100 g batch. Improved yields were observed when using electron-deficient azaheterocycles and substrates bearing electron-withdrawing substituents. 6-Chloro-1H-pyrrolo[3,2-c]pyridine was selected for further functionalization using a carbonylation protocol involving carbon monoxide. As a result, novel and promising building blocks for medicinal chemistry were obtained.
The interaction of enantiomerically pure N-tert-butylsulfinyl imines of trifluoropyruvate with diazomethane has been studied. It has been shown that there is the [3+2]-cycloaddition at the initial step with the formation of diastereomeric trifluoromethyltriazoline carboxylates in the ratio of 5.6:1. Treating the triazoline carboxylates with trifluoroacetic acid yielded optically pure aziridine carboxylates, which were subsequently converted into their corresponding acids. When subjected to hydrochloric acid in an ethereal solution, trifluoromethylaziridines underwent ring-opening and the sulfinyl group removal, producing α-chloromethylamino acids. The study also demonstrates the potential use of these aziridinecarboxylic acids in the peptide synthesis.
The host-guest complexation of cone-shaped calix[4]arene-hydroxymethylphosphonic acid (CPA) and calix[4]arene-hydroxymethyldimethylphosphine oxide (CPO) with active pharmaceutical ingredients of antiviral drugs Remdesivir, Nevirapine, Vesatolimod, and Bictegravir in the aqueous-organic mobile phase on a Zorbax CN column has been studied using RP HPLC method. By analyzing the dependence of the drug capacity values on the concentration of calixarene in the mobile phase, the stability constants (КА = 3672 - 6884 M-1) of the complexes formed have been determined. Quantum-chemical calculations show that the drugs studied form supramolecular exo-complexes with CPA and CPO molecules. These complexes are stabilized by intermolecular hydrogen bonds of proton donor groups P(O)(OH)2 CPA and proton acceptor groups Me2P=O CPO with the amino group of Remdesivir, the amide group of Nevirapine, the amino group and amide group of Vesatolimod, and the amide group of Bictegravir.
The aim of the article is to present the results of the experimental study of leachables used as primary packaging for medical devices, namely injectable implants based on hyaluronic acid. For the study, a line of injectable implants with identical qualitative composition and differing quantitative hyaluronic acid content was used. When developing the research conditions, the main characteristics of the implant gel were taken into account, and the conditions for using the appropriate medical device were modeled to obtain the most informative results and confirm the safety of the primary packaging selected. The analysis of extracts was carried out using the following methods: GC/MS, HPLC/UV/MS, ICP/MS, and IC. No substances listed as Chemicals of Potential Concern were detected in the extracts obtained, thereby confirming the safety of using the medical device for the patient under the conditions specified by the manufacturer.
A one-pot, stepwise method for the annelation of the 1,2,4-triazine core to the seven-membered 2,3-benzodiazepine ring via the interaction of the corresponding 2,3-benzodiazepin-1-yl- or 2,3-benzodiazepin-4-ylhydrazines with α-ketoesters has been developed. It has been found that a stepwise formation of an azomethine intermediate followed by solvent replacement and subsequent cyclization enables the desired compounds to be obtained in high yields. Derivatives of a new heterocyclic system of [1,2,4]triazino[3,4-a][2,3]benzodiazepine have been synthesized.
The Ukrainian school of organic dye chemistry has long received worldwide recognition. Among the scientists whose achievements embody this success is Academician Oleksandr Oleksandrovych Ishchenko. Over more than half a century of fruitful research at the Department of Color and Structure of Organic Compounds of the Institute of Organic Chemistry of the National Academy of Sciences of Ukraine, he laid the foundations for the rational design of functional dyes for light-energy conversion, particularly for various laser technologies; became one of the pioneers of polymethine ion-pair photonics; developed methodological approaches to the study of electronic absorption and fluorescence spectra using the method of moments, which provided new insights into the electronic structure of organic chromophores; and made a significant contribution to the systematic study and interpretation of the solvatochromism of polymethines of different types. The driving force behind all these achievements was his enduring passion for science — a deep desire to learn and share knowledge with future generations of researchers.
Pd nanoparticles were deposited on two different grades of activated carbon – NORIT and CAW. In addition, these carbons were pre-treated with HNO3 or covered by polyaniline, and these modified carbons were used as carriers for the Pd deposition. The resulting materials were tested as catalysts for the hydrogenation of quinoline. The best-performing samples were further tested in the hydrogenation of 4-methylquinoline. The structural features of carriers and catalysts were elucidated by the N2 adsorption studies. The grade of activated carbon was found to be a key factor controlling its performance, and the effect of the surface modification was negligible.
The review covers the latest achievements in the application of N-(tert-butylsulfinyl)polyfluoroalkyl imines in the asymmetric synthesis and summarizes stereochemical observations of their behavior in different types of reactions (reduction of the C=N bond, addition reactions with organometallic reagents, C-H acids, etc.). Fluorinated N-(tert-butylsulfinyl) imines are convenient substrates for obtaining enantiomerically enriched derivatives of polyfluoroalkyl amines, amino alcohols, amino acids, and heterocyclic systems. In recent decades, various approaches to their functionalization have been proposed. With this in mind, important aspects of their reactivity, regio- and stereochemistry have been systematized in this paper.
A method for obtaining Levosimendan suitable for industrial application has been developed. Two literature routes for the synthesis have been evaluated. It has been found that the use of enantiopure (R)-2-chloropropionyl chloride in the initial step is ineffective due to racemization at the stage of the synthesis based on the malonic ester. Instead, a reported method based on the synthesis of the Levosimendan precursor, 6-(4-aminophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one (1), from racemic 2-bromopropionyl bromide has been modified to allow for scale-up and adaptation to industrial processes. A practical resolution method has been developed to isolate the (R)-enantiomer of amine 1 from the racemic mixture with a high enantiomeric purity (the content of (R)-enantiomer is up to 99%). It has been shown that (R)-1 can be converted to Levosimendan in a high yield without the stereochemical purity loss at the chiral center.
The synthesis of pyrroles occupies a key place in synthetic organic chemistry due to the numerous biological properties of pyrrole derivatives, in particular antimicrobial, antibacterial, antifungal, antimalarial, anticancer activities, etc. Therefore, pyrroles serve as building blocks in the creation of potential pharmaceuticals and also serve as the basis for the synthesis of boradipyrromethene dyes. One of the most well-known approaches to the synthesis of pyrroles is the reaction between nitroolefins, 1,3-dicarbonyl compounds, and amines, also known as the Grob-Camenisch reaction. This review is devoted to the historical chronology from the discovery of this transformation dating back to 1950s to the present, and covers the development of various modifications of the above reaction in the synthesis of pyrroles.
