Regioselectivity in pyrazole synthesis remains a formidable challenge. This work systematically investigates the mechanisms governing the acid-catalyzed cyclization of 4,4-dimethoxybutan-2-one with methylhydrazine, tert-butylhydrazine and phenylhydrazine using a combined experimental and DFT approach. Before ketal hydrolysis, reaction predominantly occurs at the exposed C2 carbonyl carbon. Upon hydrolysis, a reactive oxocarbenium intermediate forms an ultra-deep thermodynamic trap with a Gibbs free energy change ∆G of approximately − 33 kcal/mol at the C4 site. However, the final product distribution is constrained by nucleophile-specific kinetics. For methylhydrazine, the non-negligible ketal cleavage barrier allows this unhindered nucleophile to target the protonated C2 site (+ 0.758 e) under charge control, yielding 69.8

The fine multiplet structure of the 1H NMR spectrum and the proton-coupled 15N NMR spectrum of indole was solved. A complete set of 1H–1H and 1H–15N coupling constants for [15N]indole in CD3CN solution was acquired with high accuracy. Ab initio quantum-chemical calculations of coupling constants with the DFT/B3LYP method showed a high level of agreement between the calculated and experimental values. The obtained data could serve as a reliable starting point for establishing the structure of new nitrogen-containing aromatic heterocycles.

In this work, stable chemical precursors (3,5-DTBC) and alkylated derivatives were synthesized through strategic modifications guided by the redox and chelation properties of catechol. Leveraging the molecular principle that fusing two bioactive components often yields synergistic effects, catechol — a polyphenol with broad biological activities — was integrated into the nitrogen-containing heterocyclic core structure, imidazolidine-2,4-dione, to design a novel class of hybrid compounds (7a–q) with diverse pharmacological profiles. The primary objective was to explore efficient synthetic routes, characterize structures via physicochemical analyses, and possible evaluate cytotoxicity and AT1-inhibitory activity in vitro.

Aromatic nitro compounds are important intermediates in synthetic organic chemistry. In this work, catechol was used as raw materials, and nitro‐catechol derivatives with different alkylation substitutions were synthesized using two different synthetic routes. More than 15 new previously undescribed compounds were obtained. Each compound was meticulously characterized using a suite of physicochemical techniques, with selective compounds further analyzed via X‐Ray diffraction to ascertain their structure. These newly synthesized compounds hold significant promise as candidates for further chemical modification, which underlines their potential usefulness in the field of the fine synthesis of organic compounds.

Lignin, the second most abundant natural polymer, is a by-product of the biorefinery and pulp and paper industries. This study was undertaken to evaluate the properties and estimate the prospects of using lignin as a by-product of the pretreatment of common reed straw (Phragmites australis) with deep eutectic solvents (DESs) of various compositions: choline chloride/oxalic acid (ChCl/OA), choline chloride/lactic acid (ChCl/LA), and choline chloride/monoethanol amine (ChCl/EA). The lignin samples, hereinafter referred to as Lig-OA, Lig-LA, and Lig-EA, were obtained as by-products after optimizing the conditions of reed straw pretreatment with DESs in order to improve the efficiency of subsequent enzymatic hydrolysis. The lignin was studied using gel penetration chromatography, UV-vis, ATR-FTIR, and 1H and 13C NMR spectroscopy; its antioxidant activity was assessed, and the UV-shielding properties of lignin/polyvinyl alcohol composite films were estimated. The DES composition had a significant impact on the structure and properties of the extracted lignin. The lignin’s ability to scavenge ABTS+• and DPPH• radicals, as well as the efficiency of UV radiation shielding, decreased as follows: Lig-OA > Lig-LA > Lig-EA. The PVA/Lig-OA and PVA/Lig-LA films with a lignin content of 4% of the weight of PVA block UV radiation in the UVA range by 96% and 87%, respectively, and completely block UV radiation in the UVB range.

To study the structure and dynamics of nitrogen-containing compounds, NMR parameters with directly involved nitrogen can provide valuable structure information. However, this information can only be obtained using 15N-enriched compounds due to low natural abundance of 15N and extremely short relaxation time of 14N. In the synthesis of benzamides from their 15N-ammonium salts, 15N-enriched benzamides are often used as intermediates. In the present work, we studied the dynamic structure of benzamide, which is controlled by two independent factors: hindered internal rotation of the NH2 group around the C(O)–N bond and of the amide group as a whole relative to the benzene ring. Deeper knowledge of the mechanism and parameters of these processes in amides is important for meaningful interpretation and prediction of the biological activity of aromatic amides in living systems and the strength and conformation of their supramolecular complexes with lanthanide and actinide ions. A double enriched [2H5,15N]benzamide was synthesized to avoid undesirable superposition of the strong aromatic multiplet on the amide signals in the 1H NMR spectra. The 1H NMR spectrum of this compound contained only strong signals of amide protons, which allowed accurate determination of the quantitative characteristics of the studied dynamic processes. The obtained experimental data are in good agreement with the results of quantum molecular dynamics simulation.

A method was developed for the synthesis of selectively labeled [15N]indole, allowing to obtain the target product with high chemical and isotopic purity. One-dimensional and two-dimensional 1H, 13C, and 15N NMR spectra were examined. The chemical shifts of 1H, 13C, and 15N nuclei were determined, as well as the spin-spin coupling constants of 15N nucleus and the isotopic chemical shifts of 13C nuclei for [15N]indole in CD3CN solution, caused by the replacement of 14N nucleus with a 15N nucleus. It was demonstrated that isotopic shifts of this type can provide important structural information. The NMR data set obtained in the current work can serve as an important reference point for establishing the structures of new aromatic heterocycles.

In this work, we carried out an extended verification of the 13C–15N spin–spin coupling constants as a new structural indicator of nitrogen-containing organic compounds. In this regard, we performed a quantum-chemical calculation (B3LYP with basis set 6-311++G(2df,2p)) for a representative sample of 193 spin–spin couplings for the currently known literature experimental data on them in the conformationally rigid and structurally fixed compounds. Comparison of theoretical couplings with experimental ones shows a statistically significant good to excellent agreement. A parallel analysis of the variability of the calculated values of 13C–15N spin bonds with the variability of experimental data within groups of related compounds turned out to be practically useful. The approach developed can be used to quite reasonably determine the signs of spin–spin coupling constants 13C–15N. It can also provide important additional information for assigning 13C peaks in cases where this cannot be done using standard NMR spectroscopy techniques.

Deep eutectic solvents (DESs) are an alternative to conventional organic solvents in various biocatalytic reactions. Meanwhile, there have been few studies reporting on synthetic reactions in DESs or DES-containing mixtures involving oxidoreductases. In this work, we have studied the effects of several DESs based on betaine as the acceptor of hydrogen bonds on the catalytic activity and stability of laccase from the basidial fungus Trametes hirsuta and performed enzymatic polymerization of the flavonoid dihydroquercetin (DHQ, taxifolin) in a DES–buffer mixture containing 60 vol.% of betaine-glycerol DES (molar ratio 1:2). The use of the laccase redox mediator TEMPO enabled an increased yield of DHQ oligomers (oligoDHQ), with a number average molecular weight of 1800 g mol−1 and a polydispersity index of 1.09. The structure of the synthesized product was studied using different physicochemical methods. NMR spectroscopy showed that oligoDHQ had a linear structure with an average chain length of 6 monomers. A scheme for enzymatic polymerization of DHQ in a DES–buffer mixture was also proposed.

An efficient pathway toward a novel class of trifluoromethyl building blocks was elaborated. The reaction of α-CF3-enamines with arylaldehydes resulted in direct synthesis of α,β-diaryl-CF3-enones isolated in up to 93% yield as E-isomers. The possible reaction mechanism was proposed using the Zimmerman-Traxler model. The reaction of α,β-diaryl-CF3-enones with hydrazines opens a novel pathway to trifluoromethylated pyrazolines. Oxidation of pyrazolines with DDQ opened access to totally regioselective preparation of 3-CF3-pyrazoles isolated in high yield. Using this strategy, 4-arylated derivatives of known drugs Celebrex, Mavacoxib, and SC-560 can be synthesized.

Deep eutectic solvents (DESs) are an alternative to traditional organic solvents for enzymatic reactions between compounds with poor solubility. Biocatalytic polymerization of the flavonoid (+)-catechin (CC) was carried out with laccase from the fungus Trametes hirsuta in a DES–buffer mixture (betaine/glycerol 60 vol %–buffer 40 vol %). The conditions for the synthesis of catechin oligomers (oligoCCs) soluble in organic solvents have been selected. According to the data from high-performance liquid chromatography, the oligoCCs had average molecular weights of 10 620 and 2540 g/mol with polydispersity indices of 1.1 and 1.09, respectively. The physicochemical properties of the obtained oligomers were studied via UV-visible, FTIR, 1H and 13C NMR spectroscopy. The resulting oligoCCs inhibited the α-glucosidase activity (IC50 ~ 8 μg/mL).

A method has been developed for the preparation of a new type of dispiro derivative, 5''-bromo-2-[(4-chlorophenyl)sulfanyl]-1'-methyl-1,4'-diphenyldispiro[imidazole-4,3'-pyrrolidine-2',3''-indoline]-2'',5(1H)-dione, starting from 2-thiohydantoin and using a 1,3-dipolar cycloaddition reaction. The configuration of the target dispiro derivative was unambiguously established by physicochemical methods.

Parameters of restricted internal rotation about the C–C bond of the O–C–C–N fragment in the neutral and protonated forms of noradrenaline in D 2 O, CD 3 OD, and DMSO- d 6 were estimated by quantum molecular dynamics and NMR methods. The one-dimensional internal rotation potentials were calculated in the MP2/aug-cc-pVTZ approximation. The multiplet structure of the 1 H NMR spectra of neutral and protonated noradrenaline in the given solvent series was resolved, and signals of diastereotopic methylene protons pro- S and pro- R were assigned. The conformational dependences of the proton coupling constants were calculated at the FPT-DFT 6-311++G(2 df ,2 p ) level of theory. The relative contributions of different rotamers were evaluated by solving a series of inverse vibrational problems in terms of the large-amplitude vibration model to achieve the best agreement between the calculated and experimental coupling constants. The neutral form of noradrenaline was shown to prefer conformation g + , while conformer g − was found to be the minor one. Protonation of noradrenaline molecule essentially stabilizes conformer g − . In all cases, the contribution of conformer t with transoid orientation of the oxygen and nitrogen atoms did not exceed 1%. The obtained data can be useful for the construction of a quantitative model for noradrenaline binding to receptors at the molecular level.

[3+2] Cycloaddition of CF3-ynones with azides proceeds regio-selectively to give 1-R-4-trifluoroacetyl-1H-1,2,3-triazoles as the major products.

Gold‐ and silver‐catalysed reactions of trifluoromethylated ynones with aryl (alkyl) hydrazines were investigated. The use of (THD‐Dipp)AuOTf and AgOTf resulted in quick heterocyclization reactions to selectively give 3‐CF3‐pyrazoles. AgOTf was found to be the catalyst of choice, and various 3‐CF3‐pyrazoles were formed in up to 99 % isolated yield with high regioselectivity. The reaction has a broad scope: 3‐CF3‐pyrazoles with alkyl and aryl substituents as well as different functional groups can be prepared by this approach. The known pyrazole drugs Celebrex® and SC‐560 were efficiently prepared to demonstrate the utility of the method. Mechanistic investigations revealed that the reaction involves the formation of a hemiaminal as a key intermediate.

Derivatization of the natural flavonoid dihydroquercetin with p-aminobenzoic acid was carried out in an ethyl acetate/citric buffer biphasic system using laccase from the fungus Trametes hirsuta. The main reaction product yield was ~68 mol %. The product was characterized by 1H NMR, 13C NMR, and liquid chromatography-mass spectroscopy, and its structure was elucidated. The reaction product affected viability of cultured human rhabdomyosarcoma cells (RD cell line) in a dose-dependent manner and, therefore, can be of interest to pharmaceutical industry.

Multicopper oxidases such as bilirubin oxidase (BOD) from Myrothecium verrucaria and laccase (LC) from the basidial fungus Trametes hirsuta have been used as catalysts in dihydroquercetin (DHQ) oxidative polymerization. The conditions selected enabled good yields of DHQ oligomers, which were then analyzed using UV-vis, FTIR, 1Н and 13С NMR spectroscopy. DHQ oligomers synthesized using both enzymes showed higher thermostability as compared with the monomer. Depending on the oxidase, the products of DHQ polymerization differed in physicochemical properties, and as shown by NMR studies, had different structures.