Objectives. The work set out to evaluate the energy and economic efficiency of applying complex columns with side withdrawal in extractive distillation schemes of benzene–cyclohexane–toluene mixtures of various compositions using N-methylpyrrolidone as the entrainer.

Methods. A method based on the transformation of graphs representing flowsheets was used for the synthesis of extractive distillation schemes incorporating columns with side withdrawal. Determination of optimal scheme parameters was performed by scanning the range of variable changes with a specified step according to the criterion of minimizing total energy consumption in the column reboilers. The Non-Random Two Liquid local composition equation was used for modeling vapor–liquid equilibrium. The computational experiment was carried out using the Aspen Plus v.10 software package.

Results. Six flowsheets incorporating columns with side withdrawal (flowsheets of subset I) were generated using the graph method based on five flowsheets for extractive distillation of the benzene–cyclohexane–toluene mixture incorporating columns with a side section (flowsheets of subset Θ). Optimal parameters of the synthesized flowsheets were determined for separating the studied mixture of two initial compositions according to the criterion of total energy consumption. These compositions are simplified analogs of fractions produced in the processes of catalytic hydrotreating-hydrocracking of pyrolysis gasoline (Composition 1) and during catalytic steam dealkylation of pyrolysis gasoline (Composition 2). Columns with side withdrawal in each flowsheet of subset I were calculated with both vapor-phase and liquid-phase side streams. Extractive distillation schemes of different structures were compared according to the criteria of total energy consumption in column reboilers (∑Q_reb) and total annual cost (TAC).

Conclusions. It is established that the energy and economic efficiency of flowsheets incorporating columns with side withdrawal does not significantly depend on the phase state of the side stream. When separating the benzene–cyclohexane–toluene mixture of both considered compositions, the minimum ∑Q_reb value was found to correspond to Flowsheet I2.2-V. This flowsheet consists of an extractive distillation column, an N-methylpyrrolidone regeneration column with a side withdrawal of a vapor-phase stream above the feed plate, and a distillation column for the benzene–toluene mixture. The minimum TAC value is characteristic of Flowsheet I1.1, which includes an extractive column with a side withdrawal of a stream below the feed plate in the vapor phase (for Composition 1) or in the liquid phase (for Composition 2). For separating the studied mixture of both considered compositions, it is advisable to use Flowsheet I1.1 with a liquid-phase side withdrawal stream from the extractive column, as in this case, withdrawing the side stream is simpler and regulating its flow rate and composition is easier.

Objectives. The work set out to obtain cyclic tert-amines by alkylation of dimethylaminopropylamine (DMAPA) and aminoethylpiperazine (AEP) with cis-1,4-dichloro-2-butene and cis-2,3-di(chloromethyl)-gem-dichlorocyclopropane. Quaternary ammonium salts were synthesized from a cyclic amine base and the resulting compounds evaluated as substances influencing the hemostasis process. The effect of structural fragments in the resulting substances on their anticoagulation and antiplatelet properties was evaluated.

Methods. The target compounds were obtained by a classical method of organic synthesis: by alkylation of DMAPA and AEP with cis-1,4-dichloro-2-butene and cis-2,3-di(chloromethyl)-gem-dichlorocyclopropane. The qualitative and quantitative compositions of the reaction mixtures were determined by chromatography with a Khromatek-Kristall 5000M chromatograph fitted with a 30 m × 0.25 mm × 0.5 μm capillary column containing 5% phenyl/95% polydimethylsiloxane as the stationary phase, as well as by nuclear magnetic resonance spectroscopy using a Bruker AM-500 spectrometer having operating frequencies of 500 and 125 MHz.

Results. The corresponding tertiary amines were obtained upon heating with 70–88% yield by alkylation of DMAPA and AEP with cis-1,4-dichloro-2-butene and cis-2,3-di(chloromethyl)-gem-dichlorocyclopropane. It was determined that the synthesized amines react with benzyl bromide to form salts with a yield of more than 80%. Quaternary ammonium salts were found to exhibit anticoagulation activity at the level of the reference standard, acetylsalicylic acid, and the highest activity is demonstrated by the amide 1-benzyl-4-[2-(2,5-dihydro-1H-pyrrol-1-yl)ethyl]piperazine. Analysis of the structure–property relationship showed that, in the series of DMAPA derivatives, the presence of a benzyl group increases the antiplatelet activity (the value of the maximum amplitude of platelet aggregation), whereas for the AEP derivatives, the presence of a benzyl group reduces by more than half the maximum amplitude of platelet aggregation, thereby reducing antiplatelet activity.

Conclusions. DMAPA and AEP condense with cis-1,4-dichloro-2-butene and cis-2,3-di(chloromethyl)-gem-dichlorocyclopropane to form the corresponding spirocyclic derivatives with high yields. The resulting amines are shown to undergo a quaternization reaction under thermal heating to form quaternary ammonium salts. The synthesized salts are found to exhibit anticoagulation activity comparable to that of the acetylsalicylic acid reference standard.

Objectives. The study set out to establish the scientific basis for the catalytic esterification of aliphatic carboxylic acids C₄–C₁₀ with pentaerythritol in a polar solvent, sulfolane. The kinetic parameters of the forward and reverse reactions were determined along with the influence of the carboxylic acid structure on the rate of conversion and the component composition of the reaction products.

Methods. The process was carried out in a perfectly stirred tank reactor with an excess of carboxylic acid (the molar ratio of pentaerythritol to carboxylic acid was 1 to 8, respectively) in a temperature range of 383.2–403.2 K. A combination of sulfolane and methanesulfonic acid was used as a catalytic system. This combination, which was found to be more effective as compared to the self-catalytic process, manifested in a 600–800-fold increase in the reaction rate at optimal amounts of sulfolane (30% by weight of the reaction system) and methanesulfonic acid (1% by weight of the reaction substrate). The composition of the reaction products was monitored by gas–liquid chromatography with preliminary calibration using pure substances. Chromatographic analysis was performed using a Kristall 2000M chromatograph equipped with a capillary column (60 m × 0.32 mm × 0.5 μm) with a grafted stationary phase BP-1 (100% dimethylpolysiloxane).

Results. For the first time, the parameters of the Arrhenius equation for the forward and reverse reactions of the esterification of 14 aliphatic carboxylic acids C₄–C₁₀ of various structures with pentaerythritol in a sulfolane medium were obtained. The resulting kinetic models satisfactorily describe the experimental data as confirmed by standard statistical calculation methods (in our case, the Pearson test was chosen, which is sensitive to a sufficiently large array of experimental data; the test value was at least 96%, indicating the adequacy of the kinetic model used to describe the processes). The influence of the carboxylic acid structure on the process rate and the composition of the reaction products was evaluated.

Conclusions. The conducted studies revealed that the composition of reaction products under chemical equilibrium conditions under the selected conditions is virtually independent of the structure of the carboxylic acid: the chemical reaction rate is determined primarily by the structure of the carboxylic acid. The obtained data can be used to substantiate verified kinetic models that provide the possibility of rational design of the synthesis of target esters with a high degree of selectivity and predictable properties.

Objectives. The work set out to describe the main physicochemical properties of new perfluorinated compounds (perfluoro-N-butylmorpholine, perfluoro-N-butylpiperidine, and perfluoro-N-ethylpiperidine) developed at the Russian Research Center “Applied Chemistry” (GIPH), and to evaluate the potential of their use as perfluorinated technical liquids by studying the temperature dependencies of their density, viscosity, and heat capacity in low temperature regions, as well as their applicability as media for syntheses involving strong Lewis acids using tris(pentafluoroethyl)difluorophosphorane as an example.

Methods. Perfluorinated tertiary amines (perfluorotriethylamine, perfluorotributylamine, perfluoro-N-butylmorpholine, perfluoro-N-butylpiperidine, perfluoro-N-ethylpiperidine) were synthesized by electrochemical fluorination in anhydrous hydrogen fluoride. The composition, purity, and structure of the perfluoroamines were determined by gas–liquid chromatography (Kristall 2000M) and confirmed by nuclear magnetic resonance spectroscopy (Bruker AVANCE III HD 400 MHz) and chromatography–mass spectrometry (Agilent Technologies 7890B/5977A). The thermal characteristics of the samples were determined by differential scanning calorimetry (NETZSCH DSC 214 Polyma). The density and kinematic viscosity of the samples were studied using a Stabinger viscometer (Anton Paar Stabinger Viscometer SVM 3000). Metal tris(pentafluoroethyl)trifluorophosphates were obtained by the fluorination of tris(pentafluoroethyl)difluorophosphorane by fluorides of the alkali metals—lithium, sodium, and potassium.

Results. Electrochemical fluorination produced tert-amines of various structures: perfluorotriethylamine, perfluorotributylamine, perfluoro-N-butylmorpholine, perfluoro-N-butylpiperidine, and perfluoro-N-ethylpiperidine with current yields from 29 to 61%. The dependencies of the heat capacity, density, and kinematic viscosity of new perfluorinated alkylmorpholines and alkylpiperidines in comparison with noncyclic perfluoroamines were studied over a wide temperature range. In the media of the obtained perfluoroamines, tris(pentafluoroethyl)difluorophosphorane salts of lithium, sodium, and potassium were synthesized at a yield of 38 to 95%.

Conclusions. The analysis of the physicochemical properties of heterocyclic perfluorinated tert-amines obtained in this work (perfluoro-N-butylmorpholine, perfluoro-N-butylpiperidine, and perfluoro-N-ethylpiperidine) indicates that these compounds are not inferior to noncyclic perfluorinated tert-amines in a number of characteristics, thus indicating their potential use as perfluorinated technical fluids thanks to their high heat capacity and potentially low conductivity. The key parameters determining their applicability as media for syntheses involving perfluorinated reagents are identified as physicochemical similarity, high density, and low viscosity at subzero temperatures.

Objectives. To introduce the intermediate obtained from the disposal of unusable rocket propellant—1,1-dimethyl2-methylenehydrazone (DMH)—into the synthesis of pyrroloquinolines (and pyridines) with potential applications in medicine; to carry out reactions of DMH with tetracyanoethylated ketones (TCEKs) derived from acetone, methyl ethyl ketone, cyclohexanone, 4-propylcyclohexanone, and 2-methylcyclohexanone; to investigate the prospects for increasing the yields of target products by performing the same syntheses under microwave irradiation (MWI) and using an ultrasonic reactor.

Methods. TCEKs were prepared from tetracyanoethylene (TCNE) and the corresponding ketone in dioxane, acetone, or ethanol, with the presence of concentrated hydrochloric or sulfuric acid as a catalyst. Pyrroloquinolines (and pyridines) were synthesized from DMH and the corresponding TCEK in ethyl acetate with base as a catalyst. Syntheses were carried out under standard conditions using a magnetic stirrer, an ultrasonic reactor (Vologda, Russia), and a UWave-2000 microwave reactor (Sineo Microwave Chemistry Technology Co., China). Reaction progress and product purity were monitored by thin-layer chromatography on Sorbfil plates (Sorbfil, Russia). The TCNE presence in the reaction mixture was determined by the hydroquinone test. Melting and decomposition points were measured using anOptiMeltMPA100 apparatus (OptiMelt, USA). Structural identification was performed by infrared spectroscopy (FSM-1202, SpektroLab, Russia), ¹H and ¹³C nuclear magnetic resonance spectroscopy in dimethyl sulfoxide d₆ on a Bruker AVANCE 400 WB spectrometer (Bruker Corporation, USA), and mass spectrometry using a quadrupole time-of-flight AB SCIEX TripleTOF 5600 spectrometer (AB SCIEX PTE. Ltd., Singapore) and a quadrupole gas chromatography–mass spectrometer GCMS-QP2020 NX (Shimadzu, Germany).

Results. Reliable procedures developed for the synthesis of pyrrolopyridines from acetone and methyl ethyl ketone without tar formation under ultrasonic stirring and MWI demonstrated significantly increased yields. The highest conversion of DMH to pyrroloquinoline was achieved from cyclohexanone, providing the target product in 92% yield within the shortest reaction time of 2 min under MWI conditions. However, for derivatives of 4-propylcyclohexanone and 2-methylcyclohexanone, the described synthesis modifications did not give the desired results: in the former case, a decrease in yield was observed as compared to standard methods, while in the latter, only a slight increase was obtained.

Conclusions. Ultrasonic stirring and MWI are effective for the conversion of DMH into pyrrolopyridines based on aliphatic TCEKs, but unsuitable for the synthesis of pyrroloquinolines derived from 4-propylcyclohexanone and 2-methylcyclohexanone. The high yield of pyrroloquinoline from cyclohexanone (92%) suggests potential for implementing the rapid MWI-promoted reaction between DMH and cyclohexanone-based TCEK in industrial production.

Objectives. The development of technological solutions aimed at increasing the efficiency of supercritical fluid extraction of polar biologically active substances from plant materials is a priority direction due to the demand for such substances in the food and pharmaceutical industries. The aim of this study is to develop an approach for stabilizing extractant composition by continuously feeding a polar cosolvent into a supercritical carbon dioxide flow.

Methods. The study was carried out on blackcurrant (Ribes nigrum L.) fruits, which contain polyphenols, one of the most difficultto-extract compounds. Two types of prepared raw materials were used: heat-dried at 50°C for 48 h; freeze-dried at a pressure of 68 Pa and a temperature of up to 25°C for 48 h. Extracts were obtained by supercritical fluid extraction in a 250-mL high-pressure extractor. The process was carried out at a temperature of 50°C and a pressure of 200 bar in different modes: using pure CO2; with the addition of ethanol; with the addition of acetone; and employing different methods for feeding the extractant into the high-pressure extractor.

Results. The highest efficiency of polyphenol extraction was achieved using heat drying of the raw materials in combination with a continuous supply of ethanol as a cosolvent, which enabled the highest yields of extract (22.47 wt %) and polyphenols (4.95 wt %). The experiments confirmed that the modes using acetone provide a high yield of extractive substances; however, their use is limited by the toxicity of the solvent, whereas a continuous supply of ethanol is a more promising and safer method for process intensification. Рeat-dried samples consistently demonstrated higher yields of both extract and target polyphenols in comparison with freeze-dried raw materials in all extraction modes studied.

Conclusions. The choice of drying method at the stage of raw material preparation is shown to have a significant impact on extraction efficiency: heat drying provides a higher extract yield than freeze drying. The experiments confirmed that the addition of polar cosolvents increased the solubility of polyphenols. While the highest efficiency among single-addition modes was achieved using acetone, ethanol is recommended due to its non-toxicity. By using a continuous flow of a cosolvent instead of its a single addition, the total extract yield is increased by 6.4 times, and the polyphenol content by 17 times. The proposed universal approach can be applied to the extraction of a wide range of polar compounds; even higher efficiency is expected for less polar substances.

Objectives. Current methods for testing nasal spray dosage forms during development fail to fully assess the behavior of the drug following its release from the container, including subsequent distribution, retention, and permeability across the mucosal barrier. Existing in vitro models typically overlook the critical factor of drug interaction with nasal mucus, which substantially limits their predictive power and physiological relevance. The study set out to develop a physiologically based analytical method that addresses this gap by employing representative simulated nasal mucus compositions to evaluate the key performance parameters of the spray.

Methods. The pH of the investigated compositions was determined potentiometrically in accordance with the requirements of the 15th Russian State Pharmacopoeia, OFS.1.2.3.0032, using a pH meter (Econix-Expert, Russia) equipped with an ESK-10601 glass electrode (Izmeritelnaya Tekhnika, Russia). The dynamic viscosity of the compositions was measured using a Brookfield DV2T RV rotational viscometer (Brookfield, USA) with a thermostatically controlled measuring unit ofthe coaxial cylinder type within a temperature range of 25–37°C. The contact angle was determined by the sessile drop method using an EasyDrop Standard instrument (Krüss, Germany). The distribution of nasal sprays was evaluated with a silicone model of the human nasal cavity (Koken Co. Ltd., Japan).

Results. Representative simulated nasal mucus compositions were developed and characterized that reliably reproduce the key physicochemical and rheological properties of human nasal secretions under both normal and pathologically inflamed conditions. An experimental setup combining an anatomical silicone nasal cavity model with an applied layer of simulated nasal mucus was created and validated. The developed model permits quantitative assessment of key parameters, such as the distribution and coverage area of the drug substance upon contact with mucus of varying viscosity. As such, it provides a physiologically relevant platform for studying nasal sprays during dosage form development.

Conclusions. The proposed approach offers a valuable tool for optimizing the composition and design of nasal sprays, enabling comparative analysis under conditions that closely mimic physiological realities.

Objectives. The work set out to develop epoxy multicomponent binders for polymer composite materials by interrelating the rheological properties and the curing kinetics of the epoxy modified with thermoplastic. Changes in the rheological properties of binders are determined by the competition between two processes: the curing reaction of modified epoxy oligomers with an amine curing agent, and phase separation, which leads to a loss of compatibility between thermosetting components and modifier.

Methods. During the curing process, rotational and oscillational rheometry were used. The kinetic patterns of the curing process of epoxy-amine binders based on a mixture of trifunctional and bifunctional epoxy resins modified with polysulfone were studied.

Results. The dependence of viscosity on curing time of an epoxy binder at various temperatures and polysulfone content was experimentally studied. Gelation and vitrification time, viscosity growth constants, and activation energies values were determined. It was shown that phase separation induced by curing results in the formation of a polysulfone-rich phase. Moreover, the phase separation time decreases with higher modifier content.

Conclusions. It has been established that the adding of polysulfone into the composition of a multicomponent epoxy-amine binder leads to an enhancement in the gelation time by 8–15 min, depending on the curing temperature and the thermoplastic content, which is explained by an increase in the viscosity of the binder.