Using the Paal-Knorr reaction, 1-[1-(4-methoxyphenyl)-2-methyl-5-phenyl-pyrrole-3-yl]ethanone was produced. The main stages of synthesis and yield of the target compound are described. The temperature dependence of the solubility of the synthesized compound in the temperature range 275.70-299.40 K was investigated experimentally. The use of the gravimetric method for studying solubility at atmospheric pressure in solvents of different classes is described. Using the Van't Hoff equation, the obtained data were converted to standard molar enthalpies and entropies of dissolution. The enthalpy and entropy of fusion of the obtained substance were determined by the differential thermal method. The equations for converting the research results to standard conditions (298.15 K) are given, and the results are used to calculate the thermodynamic parameters of the mixing and dissolution process of the studied ketone compound with organic solvents. The solubility of 1-[1-(4-methoxyphenyl)-2-methyl-5-phenyl-pyrrole-3-yl]ethanone in all solvents increased with increasing temperature, and these data are in good agreement with the literature data for similar substances. The interaction characteristics of the synthesized substance with solvents of different polarity were established, and the dependencies of the thermal effects of dissolution were obtained. This study of the pyrrole derivative 1-[1-(4-methoxyphenyl)-2-methyl-5-phenyl-pyrrole-3-yl]ethanone is aimed at optimizing the synthesis processes of this compound, its further purification and processing for various uses.

This paper presents the first examples of the use of arylation products of α,β-unsaturated carbonyl compounds under Meerwein reaction conditions for the synthesis of substituted 2-mercaptothiazoles. The method described here yields α-thiocyanatocarbonyl building blocks, which subsequently enable cyclization reactions with thiourea or mercaptoacetamides to synthesize the title compounds. In this way, 5-arylmethyl-2-mercaptothiazoles substituted at the 4-position and their S-substituted derivatives can be prepared very efficiently.

A simple and efficient synthetic strategy for the preparation of carbazole-basedC2-symmetric anhydrides with donor-acceptor-donor (D-A-D) architecture is presented. Four benzoic anhydrides incorporating carbazole or 3,6-di-tert-butylcarbazole donor units, linked to the anhydride acceptor moiety through either para- or ortho-positions, are rationally designed, synthesized, and systematically investigated. Photophysical studies reveal a strong dependence of photophysical properties on the linkage topology. While para-linked derivatives exhibit neither delayed fluorescence nor phosphorescence, ortho-substituted anhydrides display small singlet-triplet energy gaps and consequently show thermally activated delayed fluorescence (TADF), as well as unexpected room-temperature phosphorescence (RTP). Therefore, compounds bearing ortho-linked carbazole donor moieties are successfully employed as triplet-harvesting emitters in sky-blue organic light-emitting diodes (OLEDs), delivering electroluminescence maxima at 475 and 481 nm, maximum external quantum efficiencies of up to 21.0%, high luminance exceeding 62 000 cd/m2, and low efficiency roll-off. These results demonstrate that the formation of anhydrides from donor-substituted aromatic acids represents a versatile and effective design strategy for highly emissive TADF/RTP materials and provides a promising platform for the development of efficient multicolor OLED emitters through rational molecular engineering.

A new tandem sequence involving the Ugi reaction and Diels-Alder [4 + 2] cycloaddition based on vinylfuran and 1,3-butadienylfuran derivatives was designed and studied. It was found that in the case of 3-(furan-2-yl)acrylaldehyde, a one-pot Ugi reaction and intramolecular Diels-Alder vinylarene (IMDAV) reaction leads to the formation of the insufficiently studied furo[2,3-f]isoindole derivatives. Ugi adducts formed from (E)-3-(furan-2-yl)acrylaldehyde, maleic acid monoanilide, isonitrile, and an amine spontaneously underwent the IMDAV reaction with a high level of stereoselectivity, leading to single pairs of enantiomers of 4,4a,5,6,7,7a-hexahydro-3aH-furo[2,3-f]isoindole core in excellent yields. Under the same conditions, the (2E,4E)-5-(furan-2-yl)penta-2,4-dienal gives an Ugi adduct that undergoes the IMDA reaction without involving the furan core. The cycloaddition leads to the formation of 2,3,3a,4,5,7a-hexahydro-1H-isoindoles in high yields. The studied tandem Ugi and intramolecular Diels-Alder reactions allow high substituent variation in the named isoindoles.

In this study solubility temperature dependence of 3-(1-(4-methylphenyl)-5-phenylpyrrol-2-yl)propanoic acid in the temperature range of 271.0-318.2 K using the gravimetric method at atmospheric pressure was experimentally determined for the first time in eight organic solvents, namely methyl acetate, ethyl acetate, acetone, acetonitrile, n-propanol, isopropanol, n-butanol, isobutanol. The primary results of experimental studies of the solubility temperature dependence for each of the studied solution systems were used to calculate the standard molar enthalpy and entropy of dissolution according to the Van't-Hoff equation. The enthalpy and entropy of fusion at the melting point were determined using the results of differential thermal analysis. The equations for the recalculation of the enthalpy and entropy of fusion to a temperature of 298.15 K are presented. Using the calculated values of enthalpy and entropy of fusion to 298.15 K, the thermodynamic parameters of the process of mixing the studied acid with organic solvents were calculated. The nature of intermolecular interactions between the solvent and the dissolved substance was analysed using thermodynamic parameters of mixing. The present study contains fundamental thermodynamic values that are of practical importance for the optimisation of processes of synthesis, processing and purification of the investigated N-substituted derivative of 3-(5-phenylpyrrol-2-yl)propanoic acid.

A first application of 2-(methoxycarbonyl)thiophen-3-diazonium salts in the halothienylation of α,β-unsaturated functionalized compounds under Meerwein reaction conditions is presented. This process provides thiophene-containing building blocks that can then undergo cyclization reactions with bisnucleophiles to synthesize thiophene-3-yl-containing heterocyclic systems. In this way, substituted 2,3′-bithiophene compounds and thiophene-3-yl derivatives of 2-aminothiazole, 2-aminoselenazole, thiazolidine, and selenazolidine can be efficiently prepared.

A combined experimental and theoretical study of the fundamental thermodynamic parameters of 3-(5-phenyl-1-(pyridin-3-yl)-1H-pyrrol-2-yl)propanoic acid was carried out for the first time. The enthalpies of combustion, formation in the condensed state, fusion, and vaporization were determined using high-precision equipment. Based on the experimentally obtained results, the enthalpies of sublimation and formation in the gaseous state at 298.15 K were calculated using two methods. The possibility of applying analytical methods of Domalski, Joback and quantum chemical calculations to determine the enthalpy of formation in the gas phase is analysed.

For the first time, the temperature dependence of the solubility of 3-(1,5-diphenylpyrrol-2-yl)propanoic acid was experimentally determined in eight organic solvents (methyl acetate, ethyl acetate, acetone, acetonitrile, n-propanol, isopropanol, n-butanol, and isobutanol) within the temperature range of 275.5–322.0 K at atmospheric pressure. Based on the solubility data, the enthalpies and entropies of solvation were calculated. Using differential thermal analysis, the enthalpy of fusion at the melting point (Tfus=442.41.5К) was determined. The equations for recalculating the enthalpies and entropies of fusion to 298 K are presented. The thermodynamic parameters of the mixing process of 3-(1,5-diphenylpyrrol-2-yl)propanoic acid with the solvents were also calculated. A compensation effect in the thermodynamic parameters of mixing was established, and the nature of the interactions between the solvent and the dissolved substance was analyzed.

A novel application of 1-methylpyrazol-3-yldiazonium salts in the Meerwein reaction was introduced. These diazonium salts reacted with α,β-unsaturated functionalized compounds under Meerwein reaction conditions to yield pyrazole-containing building blocks, which subsequently allowed cyclization reactions with bisnucleophiles for the synthesis of pyrazol-3-yl-containing heterocyclic systems. In this way, pyrazole-containing heterocyclic compounds with 2-aminothiazole, 2-aminoselenazole, thiazolidin-4-one, selenazolidin-4-one, 3-hydroxythiophene, and 3-aminothiophene rings were efficiently prepared.

For the first time, an experimental determination of the main (basic) thermodynamic properties of 3-(5-phenylpyrrol-2-yl)-propanoic acid was carried out using differential thermal and thermogravimetric methods of analysis and combustion bomb calorimetry. The values of the enthalpy of sublimation at 298 K and the enthalpy of formation in the gaseous state were calculated using the values of the enthalpies of vaporization and fusion, which were recalculated to 298 K, and the enthalpy of formation in the condensed state. The applicability of the Domalsky additive method for calculating the enthalpies of formation in the condensed and gaseous states is shown. Thermodynamic parameters will be crucial in the development of technological processes for the synthesis, purification, use, storage and transportation of 3-(5-phenylpyrrol-2-yl)-propanoic acid, as this compound exhibit biological activity, evidenced by the preliminary assessment of the molecule structure using the web-based program SuperPred, and will have potential use in the production of medicines.

A series of new azomethines with pyrazole and arylfuran fragments – 4-[{(5-Arylfuran-2-yl)methylene}amino]-1,2-dihydro-1,5-dimethyl-2-phenyl-3H-pyrazol-3-one – are synthesized by the condensation of 4-aminoantipyrine and 5-arylfurfural using a Monowave 50 synthesis reactor. The structures of the obtained compounds are confirmed with 1H NMR and IR spectroscopy.

To enhance the usually low-charge carrier mobilities of highly twisted donor-acceptor-type compounds that exhibit thermally activated delayed fluorescence, we designed a rodlike acceptor benzodioxinoquinoxaline. This acceptor and two donor-acceptor-donor derivatives were synthesized via microwave Buchwald-Hartwig cross-coupling reactions with yields of up to 91%. The compounds exhibit three different types of photoluminescence, which is well-explained by quantum chemical calculations. Benzodioxinoquinoxaline shows blue fluorescence, with a very short lifetime of 0.64 ns. Its derivatives exhibit either green solid-state-enhanced thermally activated delayed fluorescence (SSE-TADF) or room-temperature phosphorescence (RTP) with lifetimes approaching 7 ms. When molecularly dispersed in a polymeric host, the compounds show a photoluminescence quantum yield close to 60%. The derivatives containing acridine or phenoxazine moieties exhibit bipolar charge transport. At an electric field of 5.8 × 105 V/cm, hole and electron mobilities of the phenoxazine-containing compound reach 3.2 × 10-4 and 1.5 × 10-4 cm2 V-1 s-1, respectively. Among the studied SSE-TADF-based organic light-emitting diodes, the device containing this compound shows the highest external quantum efficiency of 12.3% due to the good charge-transporting and SSE-TADF parameters of the emitter.

The synthesis of four 4-(carbazolyl-R-benzoyl)-5-CF3-1H-1,2,3-triazoles with extra groups ((3-methyl)-phenyl-, 4-fluorophenyl-, quinolinyl-, or (3-trifluoromethyl)-phenyl-) in the acceptor fragment has been reported. The effects of substituents with different electron-withdrawing strengths on the thermal, electrochemical, photophysical, and electroluminescence properties of the synthesized compounds are discussed. The results of X-ray analyses and density functional theory (DFT) calculations support unusual molecular packing and electronic properties. The compounds are capable of glass formation with glass transition temperatures ranging from 54-84 °C. Ionization potentials of the compounds are in the range of 5.98-6.22 eV and electron affinities range from 3.09 to 3.35 eV. Under ultraviolet excitation, the neat films of the compounds exhibit blue emission with photoluminescence quantum yields ranging from 18 to 27%. The films of selected compounds are used for the preparation of host-free light-emitting layers of organic light-emitting diodes with very simple device structures and an external quantum efficiency of 4.6%.

This review is devoted to the synthesis and application of fluoro-substituted 1,2,3-triazoles. The analysis of the available studies of fluorinated triazoles indicates exceptional value properties especially for biomedical research, despite the significant limitations of synthetic methods of their preparation. In general, it can be noted that today there are only two strategic approaches to obtaining fluorinated triazoles. First, Huisgen 1,3-dipolar cycloaddition, which is significantly limited by stability problems of fluorine-unsaturated dipolarophiles, regioselectivity and low conversion problems. This approach allows preferentially obtaining 4-fluoro-1-substituted triazoles. Second, nucleophilic substitution, which allows obtaining 5-fluoro-1,4-disubstitution, but under rather hard conditions and is also limited by the nature of the substituent. Finally, there are practically no protocols for the preparation difluorotriazoles, and, also, the use of fluoro-substituted 1,2,3-triazoles as regents for further transformations is not enough studied. The analysis of the available studies of fluorinated triazoles indicates exceptional value properties, especially for biomedical research, despite the significant limitations of synthetic preparation methods. In general, it can be noted that today, there are only two strategic approaches to obtaining fluorinated triazoles - Huisgen 1,3-dipolar cycloaddition and nucleophilic substitution.image

In this study, the temperature dependences of the solubility of 5-(4-methylphenyl)-2- furanpropanoic acid in various solvents were evaluated: methyl and ethyl acetate, acetonitrile, propane-1-ol, and propan-2-ol. The results of the analysis are presented in the form of linear equations according to the Schröder model, which allowed us to determine the enthalpies, entropies, and Gibbs energies of solubility at a temperature of 298.15 K. The melting points of the acid were determined using the method of differential thermal analysis, which allowed us to calculate the enthalpies, entropies, and Gibbs energies of mixing.

A number of new functionalized 4,5-dihydropyrazolo[1,5- a ]thieno[3,2- e ]pyrimidine derivatives were obtained by the domino reaction of thienylhydrazonyl chlorides with (1,2,4-oxadiazol-5-yl)acetonitrile. In organic synthesis, much attention has been recently paid to tandem and domino reactions. The advantage of such reactions concerns high selectivity, ease of performance, reduction of the number of intermediate steps, high atom economy. In this work, we have investigated a new domino reaction of ortho -carboxyl-containing nitrileimines with 2-(3-aryl-1,2,4-oxadiazol-5-yl)acetonitrile. In the reactions, nitrileimines are generated in situ from the corresponding hydrazonyl halides by base action. Thienylhydrazonyl chlorides 3a,b , the precursors of nitrileimines, were obtained according to the classical scheme of interaction of 2-chloro-3-oxobutanoate with the corresponding diazonium salts 2a,b . Thienylhydrazonyl chlorides 3a,b reacted with 2-(3-aryl-1,2,4-oxadiazol-5-yl)acetonitriles 4a-e in methanol solution in the presence of two equivalents of sodium methylate at room temperature. The target 5-oxo-3-(3-aryl-1,2,4-oxadiazol-5-yl)-4,5-dihydropyrazolo[1,5- a ]thieno[3,2- e ]pyrimidines 5a-e were obtained by stirring the reaction mixture for 12 h. The long reaction time caused the side reactions on the ester group of the formed pyrazolo[1,5- a ]thieno[3,2- e ]pyrimidines. Thus, in the case of using thienylhydrazonyl chloride 3a with a methyl substituent in the thiophene ring, products 5a,b were isolated from the reaction mixture, which underwent transesterification. Whereas in the case of using thienylhydrazonyl chloride 3b with a cyclohexyl substituent in the thiophene ring, a mixture of methyl and ethyl esters (which are difficult to separate into individual components) was isolated from the reaction mixture. Therefore, in this case, the reaction mixture was diluted with water, if necessary, an alkali solution was added so that the pH of the solution was 11−12, and heated until the precipitate dissolved, then the concentrated hydrochloric acid was added to the hot solution in a strongly alkaline medium, and the formed precipitate was left to crystallize, filtered off to give 3-(1,2,4-oxazol-5-yl)-5-oxo-4,5-dihydropyrrolo[1,5- a ]thieno[3,2- e ]pyrimidin-2-carboxylic acids 5c-e . The reaction proceeds according to the domino principle: at the first stage, 1,3-dipolar cycloaddition takes place with the formation of intermediate 5-amino- 1H -pyrazoles, which undergo spontaneous intramolecular cyclization with the participation of ester and amino groups to form a pyrimidine cycle. Keywords : thienylhydrazonyl chlorides, 1,2,4-oxadiazole, 4,5-dihydropyrazolo[1,5- a ]thieno[3,2- e ]pyrimidines, domino reaction, 1,3-dipolar cycloaddition.

A convenient two-step method for the synthe-sis of novel 1,3-benzoxathiol-2-ones and naphtho[2,1-d][1,3]oxathiol-2-ones bearing (1H-tetrazol-1-yl)phenyl motif was developed. As a key step of the synthesis, an arylation of quinones (1,4-benzoquinone, 1,4-naphtho-quinones) with the (1H-tetrazol-1-yl)arenediazonium salts was studied and efficient protocols were elaborated to obtain a variety of substituted ((1H-tetrazol-1-yl)phenyl) benzo/naphtho-1,4-quinones in good to excellent yields. An alternative synthesis of ((1H-tetrazol-1-yl)phenyl) naphtho-1,4-quinones via Diels-Alder reaction of tetrazolylphenyl-1,4-benzoquinones was demonstrated. The prepared benzo/naphtho-1,4-quinones readily react with thiourea at room temperature in the presence of a strong mineral acid to form intermediate isothiuronium salts, which cyclize with high yields to condense 1,3-oxathiol-2-ones under heating.

Previously, we discovered that N-(5-benzyl-1,3-thiazol-2-yl)-4-(5-methyl-1H-1,2,3-triazol-1-yl)benzamide possessed a remarkable cytotoxic effect on 28 cancer cell lines with IC50 < 50 μM, including 9 cancer cell lines, where IC50 was in the range of 2.02-4.70 μM. In the present study, we designed a novel N-(5-benzylthiazol-2-yl)amide compound 3d that was synthesized using the original bioisosteric replacement of 1H-1,2,3-triazole ring by the 1H-tetrazole ring. A significantly enhanced anticancer activity in vitro with an excellent anti-leukemic potency towards chronic myeloid leukemia cells of the K-562 line was demonstrated. Two compounds - 3d and 3l - were highly cytotoxic at nanomolar concentrations towards various tumor cells of the following lines: K-562, NCI-H460, HCT-15, KM12, SW-620, LOX IMVI, M14, UACC-62, CAKI-1, and T47D. As a highlight, the compound N-(5-(4-fluorobenzyl)thiazol-2-yl)-4-(1H-tetrazol-1-yl)benzamide 3d inhibited the growth of leukemia K-562 cells and melanoma UACC-62 cells with IС50 of 56.4 and 56.9 nM (SRB test), respectively. The viability of leukemia K-562 and pseudo-normal HaCaT, NIH-3T3, and J774.2 cells was measured by the MTT assay. Together with SAR analysis, it allowed the selection of a lead compound 3d, which demonstrated the highest selectivity (SI = 101.0) towards treated leukemic cells. The compound 3d caused DNA damage (single-strand breaks detected by the alkaline comet assay) in the leukemic K-562 cells. The morphological study of the K-562 cells treated with compound 3d revealed changes consistent with apoptosis. Thus, the bioisosteric replacement in (5-benzylthiazol-2-yl)amide scaffold proved to be a perspective approach in the design of novel heterocyclic compounds with enhanced anticancer potential.

An important way of forming the indole cycle is the Nenitsescu reaction. Convenient precursors for this reaction are readily available β-ketoesters or 1,3-diketones, which after conversion to enamines react with 1,4-quinones to form polysubstituted indoles. The regio- and chemoselectivity of the interaction depends on the conduction conditions, the structure of the quinone and enamine component, and the electronic effects of the substituents. Studies have shown that the condensation of quinones with enamines can take place in at least a few main directions. The most common are 5- or 6-hydroxyindoles, 5-hydroxybenzofurans and 5-hydroxyindazoles. However, the synthetic potential of the reaction is not limited to this, because it also allows to obtain other, more diverse structures that are difficult to access in other ways – benzocarbazoles, pyrido- [2,3- b ]indoles, furo[3,2- h ]indoles, furo[2,3- g ]indoles, imidazo[4,5- g ]indoles, dihydro-benzo[ g ]indoles, pyrrolo[2,3- h ]quinolines. However, interest in this reaction has not diminished to this day, as it is a convenient method of forming a base fragment for many biologically active substances. In this paper, we describe the results of studies obtained during the study of the reactivity of monoarylquinones to enamines derived from cyclic ketones and secondary amines. With the use of such enamines, it is impossible to obtain indoles by the Nenitsescu reaction, so the formation of benzofuran derivatives was expected, but the question of regioselectivity of the process remained open. It was found that the interaction of 1-morpholino-1-cyclohexene 6 with 2-aryl-1,4-benzoquinones 1 – 5 at room temperature in a dry benzene forms 4-aryl-5a-morpholin-4-yl-5a,6,7,8,9,9a-hexahydrodibenzo[ b , d ]furan-2-oles 7 – 11 . The reaction was found to be regioselective – of the three possible regioisomers, only 4-aryl-substituted dibenzofurans were formed, and no indole cyclization products were detected. The structures of the synthesized compounds were confirmed by the 1 H-, 13 C NMR spectroscopy and element analysis data. Keywords: 2-aryl-1,4-benzoquinones, 1-morpholino-1-cyclohexen, enamines, Nenitzescu reaction, dibenzo[ b , d ]furan-2-ones, heterocycles.