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The paper presents the results of the study of the process of electrophilic intramolecular cyclization of 3-methyl(phenyl)-2-(prop-2-yn-1-ylthio)-7-(trifluoromethyl)quinazolin-4(3H)-ones by tellurium tetrahalides. 3-Methyl(phenyl)-2-(prop-2-yn-1-ylthio)-7-(trifluoromethyl)quinazolin-4(3H)-ones were prepared by the alkylation of the corresponding thions with propargyl bromide in an alkaline alcohol medium. It is found that the interaction of propargyl thioethers of 3-substituted 2-thioxo-7-(trifluoromethyl)-2,3-dihydroquinazolin-4(1H)-ones with tellurium tetrahalides, which were obtained in situ from tellurium dioxide and six equivalents of corresponding concentrated hydrohalic acid, leads to the formation of halides of angular 4-methyl(phenyl)-5-oxo-1-((trihalotellanyl)methylidene)-8-(trifluoromethyl)-1,2,4,5-tetrahydrothiazolo[3,2-a]quinazolin-10-iums. The most optimal conditions for the tellurium-induced electrophilic heterocyclization of propargyl thioethers with tellurium terahalides are the use of glacial acetic acid as a solvent and stirring of the reaction mixture at room temperature for 24 hours. It is found that the electrophilic cyclization of 3-methyl(phenyl)-2-(prop-2-yn-1-ylthio)-7-(trifluoromethyl)quinazolin-4(3H)-ones by tellurium tetrahalides occurs stereoselectively with the formation of one configurational isomer. The influence of the nature of halogen in the electrophilic reagent and the substituent in position 3 of quinazoline is examined and it is found that these factors do not affect the regioselectivity of the electrophilic intramolecular cyclization process. As a result of the conducted study, potentially biologically active salts of tellurofunctionalized thiazolinoquinazolines of angular structure were received.

It is known from the literature, that organic tellurium compounds have valuable biological properties. One example of such type of compounds is organic ditellurides. There are also known the usage of ditellurides as initiators in the synthesis of polymers, and they are widely used as synthons for the synthesis of another organotellurium compounds. In particular, the halogenation of diarylditellurides leads to the formation of such electrophilic reagents as aryltellurium trihalides, which proved to be suitable substrates for the synthesis of heterocyclic compounds. This paper describes a method for the synthesis of ditellurides, which contain condensed heterocycles of the quinazoline and thienopyrimidine series, by reducing of the corresponding heteryltellurium trichlorides. The interaction of 2-methyl-2-(trichlorotelluromethyl)-2,3-dihydro-5 H -thiazolo[2,3- b ]quinazolin-5-one hydrochloride with a 4-fold excess of 9-aqueous sodium sulfide in water at room temperature leads to formation of 2,2'-(ditellanidylbis(methylene))bis(2-methyl-2,3-dihydro-5 H -thiazolo[2,3- b ]quinazolin-5-one) with high yield. The introduction of the trifluoromethyl group at the 8 th position of 2-methyl-2-(trichlorotelluromethyl)-2,3-dihydro-5 H -thiazolo[2,3- b ]quinazolin-5-one hydrochloride increases the yield of the target ditelluride. 2-[(Trichlorotelluro)methyl]-2,3,6,7,8,9-hexahydro-5 H -benzo[4,5]thieno[2,3- d ]thiazolo[3,2- a ]pyrimidin-5-one hydrochloride was used for the study of the impact of the condensed with pyrimidine moiety cycle on the formation of ditellurides in the sodium sulfide reduction reaction and it was stated that under the found conditions it is uniformly converted into 2,2'-(ditellanidylbis(methylene))bis(2,3,6,7,8,9)-hexahydro-5 H -benzo[4,5]thieno[2,3- d ]thiazolo­[3,2- a ]-pyrimidin-5-one). The obtained ditellurides were used in the bromination reaction. It was found that the interaction of the starting ditellurides with a triple excess of bromine in chloroform medium allows obtaining the tribromides of the thiazoloquinazoline and thiazolothienopyrimidine series selectively. Therefore, the hydrochlorides of trichlorotelluromethyl-substituted thiazolinopyrimidines can be reduced to bis heterylditellurides, which under bromination conditions form tribromotelluromethyl-substituted thiazolinopyrimidines.

Quinoline and its derivatives represent the important class of nitrogen-containing heterocycles, which are useful intermediates in organic synthesis and exhibit a wide range of biological activity. In addition, the quinoline nucleus is a part of natural alkaloids and drugs that is why the synthesis of new quinoline derivatives is an actual task. The 2-chloroquinoline-3-carbaldehyde pays particular attention among a number of quinolines, which contains a chlorine atom and an aldehyde group, which make it an universal intermediate syntone in the synthesis of various bioactive quinoline derivatives. The purpose of this work is to synthesize Schiff bases based on 2-chloroquinoline-3-carbaldehyde. It was found that the interaction of 3-formyl-2-chloroquinoline with 1-aminopropanol-2 in an alcohol medium occures with the formation of 1-((2-chloroquinolin-3-yl) methylene) amino)propan-2-ol. To determine the impact of the nature of the alkyl substituent near the amino group, the condensation reactions of 2-chloroquinoline-3-carbaldehyde with amines containing cycloheptyl and cyclohexenyl fragment were performed. As results, Schiff bases with good yields (63%, 67%) have been received. The changing the alkyl substituent on the aromatic fragment in the amine molecule can increase the yields of the target azomethines to 75-97%. The use of amines with a heterocyclic moiety in the condensation reaction does not significantly impact on the yield of imines (71-77%). For further functionalization, the interaction of 1-(2-chloroquinolin-3-yl)-N-(4-fluorobenzyl)methanimine with 1,2,3,4-tetrahydroquinoline in ethyl alcohol has been performed. It results in 1-(3,4- dihydro-2H-[1,2'-biquinolin]-3'-yl)-N-(4-fluorobenzyl)methanimine, which contains two quinoline rings in its composition. The 3-(((2-chloroquinolin-3-yl)methylene)amino)tetrahydrothiophene 1,1-dioxide was converted to 3-((tetrazolo[1,5-a]quinolin-4-ylmethylene)amino)tetrahydrothiophene 1,1 -dioxide via reacting of the corresponding imine with sodium azide in dimethyl sulfoxide. Thus, bioperspective functionalized quinolines with imine, amine and azide moieties have been synthesized.

3-Phenyl-2-(prop-2-en-1-ylsulfanyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one reacted with 4-methoxyphenyltellurium trichloride in a regioselective manner to give angularly fused 1-{[dichloro(4-methoxyphenyl)-λ4-tellanyl]methyl}-4-oxo-5-phenyl-1,2,4,5,6,7,8,9-octahydrobenzo[4,5]thieno[3,2-e][1,3]thiazolo[3,2-a]pyrimidinium chloride. Electrophilic cyclization of 2-(prop-2-en-1-ylsulfanyl)- and 2-(2-methylprop-2-en-1-ylsulfanyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-ones with 4-methoxyphenyltellurium trichloride afforded linearly fused 3-{[dichloro(4-methoxyphenyl)-λ4-tellanyl]methyl}-2,3,6,7,8,9-hexahydro-5H-benzo[4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidin-5-one hydrochlorides. Regardless of the reactant ratio, the products were isolated as 1:1 complexes with 4-methoxyphenyltellurium trichloride.

It is known that the quinazoline fragment is a structural element of many natural alkaloids. A promising method for the synthesis of condensed derivatives of quinazoline is the method of electrophilic intramolecular heterocyclization. The purpose of this work is to investigate the regioselectivity of electrophilic heterocyclization of S-allyl derivatives of quinazolone with aryltellurium trichlorides. N-(3)-phenyl-2-S-alkenyl derivatives of quinazolone with a non-terminal allyl substituent are used as substrates for aryltellurohalogenation. The choice of such objects is motivated by the presence of one additional nucleophilic center for cyclization – the endocyclic nitrogen atom in the first position of the pyrimidine cycle. Interaction of allyl(methallyl) substituted thioquinazolones with p methoxyphenyltellurium trichloride was carried out in acetic acid or tetrahydrofuran (THF) at room temperature for 8 hours stirring the reaction mixture. It has been established that irrespective of the ratio of reagents, the non-terminal alkenyl thioether, under the action of p-methoxyphenyltellurium trichloride, undergoes annulation of the thiazoline ring to form tricyclic condensed systems of the angular structure. It should be noted that the molecular complex of p-methoxyphenyltellurium trichloride with Sulfur atom of thiazolinoquinazolone is formed. The formation of such a complex was not observed under aryltellurohalogenation of N-alkenyl 2-thioxoquinazolones, where, obviously, there is intramolecular coordination of the Sulfur atom to the Tellurium atom. Instead, the use of the terminal-substituted dimethylallyl thioether in the reaction with p methoxyphenyltellurium trichloride in similar conditions changes the direction of the reaction and leads to the formation of the molecular complex. The impossibility of the cyclization is due to the steric shielding of the reaction center with respect to the tellurim-containing electrophile. Thus, thioethers of quinazolone with a terminal non-substituted allyl substituent under the action of p-methoxyphenyltellurium trichloride undergo cyclization, while the introduction of two methyl groups to the terminal carbon atom of the allyl fragment changes the direction of the reaction and leads to the formation of the molecular complex.

Піримідинон входить в склад біоактивних природних сполук, таких як урацил, тимін та цитозин. Похідні піримідинону проявляють протипухлинні, антивірусні та психотропні властивості. При гетероциклізації ненасичених похідних піримідинтіонів утворюються конденсовані азолопіримідини, які також проявляють широкий спектр біологічної активності. Введення до складу таких систем атома Телуру може підвищити їх біоактивність. Одним з найзручніших та найпростіших методів введення атома Телуру є метод електрофільної внутрішньомолекулярної циклізації.Взаємодію між вперше синтезованим 3-металіл-2-тіоксопіримідин-4-оном та п-метоксифенілтелуртрихлоридом проводили в льодяній оцтовій кислоті при кімнатній температурі. Встановлено, що електрофільна внутрішньомолекулярна циклізація N-металіл 2-тіоксопіримідин-4-ону п-метоксифенілтелуртрихлоридом проходить за участю атома Сульфуру з анелюванням тіазолінового циклу до піримідинової системи. В результаті реакції отримано 2,7-Диметил-2-{[дихлоро(4-метоксіфеніл)-телуро]метил}-2,3-дигідро-5H-[1,3]тіазоло[3,2-a]піримідин-5-он гідро хлорид.Регіоселективность процесу електрофільної циклізації арилтелуртрихлоридом досліджували на 2-S-алкенільних похідних 6-метилпіримідин-4-ону. Показано, що реакція між арилтелуртелуртрихлоридом та 2-тіоалкенільними похідними 6-метилпіримідин-4-ону в знайдених умовах приводить до утворення продуктів циклізації із залученням атома Нітрогену в третьому положенні піримідину. Виявлено, що утворюються телурофункціоналізовані тіазолінопiримідини у вигляді комплексів з арилтелуртрихлоридом. Для вивчення впливу халькогену на регіоселективність процесу електрофільної циклізації в реакції з п-метоксифенілтелуртрихлоридом використано металільний селеноетер 6-метилпіримідин-4-ону. Доведено, що 2-Se-металільний N-1,3-незаміщений піримідинон циклізується арилтелуртрихлоридом з утворенням селеназолінопіримідинової системи, що в свою чергу дозволяє отримувати потенційно біологічно активні гетероцикли з ендоциклічним атомом Селену та екзоциклічним атомом Телуру. Природа халькогену не впливає на напрямок електрофільної внутрішньомолекулярної циклізації. Будову отриманих сполук доведено ЯМР-спектроскопією, ІЧ-спектроскопією та елементним аналізом., Pyrimidinone is a component of bioactive natural compounds such as uracil, thymine and cytosine. Pyrimidinone derivatives exhibit antitumor, antiviral and psychotropic properties. The heterocyclization of unsaturated pyrimidinetione derivatives produces condensed azolopyrimidines, which also exhibit a wide range of biological activity. The introduction а tellurium atom into such systems can increase their bioactivity. One of the most convenient and straightforward methods for introducing a tellurium atom is the electrophilic intramolecular cyclization method.The interaction between synthesized for the first time 3-methyl-2-thioxopyrimidin-4-one and p-methoxyphenyltellurium trichloride was carried out in glacial acetic acid at room temperature. It has been established that the electrophilic intramolecular cyclization of N-methallyl 2-thioxopyrimidine-4-one p-methoxyphenyltellurium trichloride takes place with the participation of a sulfur atom with the anelation of the thiazoline cycle to the pyrimidine system. As a result of reaction received 2,7-Dimethyl-2-{[dichloro(4-methoxyphenyl)-telluro]methyl}-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidine-5-one hydrochloride.The regioselectivity of the process of electrophilic cyclization with aryltelluriumtrichlotide was investigated on 2-S-alkenyl derivatives of 6-methylpyrimidin-4-one. It is shown that the reaction between aryltellurium trichloride and 2-thioalkenyl derivatives of 6-methylpyrimidin-4-one results in the formation of cyclization products with the involvement of a nitrogen atom at the third position of the pyrimidine. It is revealed that tellurofunctionalized thiazolinopyrimidines are formed in the form of complexes with aryltellurium trichloride. To study the effect of chalcogen on the regioselectivity of the process of electrophilic cyclization in reaction with p-methoxyphenyltellurium trichloride, a metalyl selenoether of 6-methylpyrimidin-4-one was used. It has been proved that 2-Se-methallyl N-1,3-unsubstituted pyrimidinone is cyclized by aryltellur trichloride to form a selenazolinopyrimidine system, which in turn allows to obtain potentially biologically active heterocycles with an endocyclic Selenium atom and an exocyclic Tellurium atom. The nature of chalcogen does not affect the direction of electrophilic intramolecular cyclization. The structure of obtained compounds were proved by NMR spectroscopy, IR spectroscopy and elemental analysis.

Electrophilic heterocyclization of 5,6-disubstituted 3-alkenyl-2-thioxothieno[2,3-d]pyrimidin-4-ones by treatment with p-alkoxyphenyltellurium trichlorides leads to annulation of the thiazoline moiety with the formation of 6,7-disubstituted-2-[dichloro-(p-alkoxyphenyl)telluromethyl]-2,3-dihydro-5Н-[1,3]thiazolo[3,2-а]thieno[2,3-d]pyrimidin-5-one hydrochlorides.

The derivatives of quinazolines and their fused analogues are promising objects for the rational design of biologically active compounds as prototypes for innovative medicines. This is due to the fact that the quinazoline fragment is a structural unit of many natural alkaloids. Electrophilic intramolecular heterocyclization is a promising method for the synthesis of fused derivatives of quinazoline.This research is devoted to the synthesis of new functionalized unsaturated condensed derivatives of quinazolin-4-one and the study of the regio chemistry of the process of electrophilic heterocyclization under the action of tellurium tetrachloride. The choice of such an electrophilic reagent is due to the fact that in recent years the organic synthesis of chalcogen-containing compounds, in particular, tellurium compounds that exhibit a wide range of biological activity, is increasingly developing.It was established that the electrophilic intramolecular cyclization of 3-alkenyl-2-thioquinazolin-4-one under the action of tellurium tetrachloride in an aqueous acetic acid medium at room temperature takes place with the participation of the alkenyl moiety and the exocyclic sulfur atom in the second position of quinazoline. As a result, thiazolidinequinazoline systems of linear structure were obtained. The structure and composition of the obtained tellurium-containing hydrochlorides has been proved by 1H, 13C NMR spectra and elemental analysis. In the PMR spectrum of hydrochlorides, signals of aliphatic cyclic methylene and methine groups and of the acyclic trichlorotellanylmethyl group are observed, which, together with the signals of aromatic protons, indicates on the formation of thiazolidinequinazolones. The absence of signals characteristic of the C=S group and presence of signals typical for the C-S bond in the 13C NMR spectra are in accord with the proposed structure of the cyclization products.Thus, we investigated the regio chemistry of the electrophilic intramolecular cyclization of 3-alkenyl-2-thioquinazolin-4-one under the action of tellurium tetrachloride. It was proved that the annelation of the thiazolidine cycle takes place with the participation of the sulfur atom in the second position of the pyrimidine, with the formation of tricyclic hydrochlorides of linear structure.

Derivatives of pyrazolo[3,4-d]pyrimidine have valuable biological activity. The structural fragment of pyrazolopyrimidines is widely used to develop new effective pharmaceuticals. A new promising direction in the construction of polycyclic systems based on pyrazolopyrimidine is the method of electrophilic intramolecular heterocyclicization.The halogenation of 5-methyl-6-thioxopyrazolo[3,4-d]pyrimidin-4-one was carried out in acetic acid medium at room temperature with twice the excess of halogen. It was found that halogenation (with bromine and iodine) of 5-methyl-6-thioxopirazolo[3,4-d]pyrimidin-4-one results the annelation of the thiazolinic cycle with the formation of linear polynuclear systems of a salt-like structure. 7-Halogenomethyl-7-methyl-1,4,6,7-tetrahydropyrazolo[3,4-d][1,3]thiazolo[3,2-a]pyrimidin-4-one was obtained via the action of sodium sulfite in the DMSO-water medium.To study the effect of the nature of the electrophilic reagent on the direction of the electrophilic intramolecular cyclization of 5-methyl-6-thioxopyrazolo[3,4-d]pyrimidin-4-one the p-methoxyphenyltetrachloride was used (tested). Electrophilic heterocyclization take place under similar conditions (room temperature, glacial acetic acid medium), with the formation of the tricyclic system with an exocyclic aryltellurium moiety – 7-(dichloro-(4-methoxyphenyl) telluromethyl)-7-methyl-1,4,6,7-tetrahydropyrazolo[3,4-d][1,3]thiazolo[3,2-a]pyrimidin-4-one. Thus, the direction of electrophilic intramolecular cyclization of 5-methyl-6-thioxopyrazolo[3,4-d]pyrimidine-4-one using as electrophilic agents of halogens (bromine, iodine) and p-methoxyphenyltetrachloride does not depend on the nature of the electrophile and takes place with the participation of the exocyclic sulfur atom in the second position of the pyrimidine and lead to the formation of a condensed system of linear structure – halogenomethyl or aryl telluromethyl derivatives of pyrazolo[3,4-d][1,3]thiazolo[3,2-a]pyrimidin-4-one. The composition and structure of all synthesized compounds were proved by elemental analysis and 1H-NMR spectra.

It is known from the literature that electrophilic heterocyclization of unsaturated substrates under the action of aryltellurium trichlorides is widely used to obtain tellurium-containing polycondensed heterocyclic systems, whereas the use of p -alkoxyphenyltellurium tribromides in such reactions is almost not described. p -Ethoxyphenyltelluriumtribromide was used for study the influence of a halogen in the electrophilic aryltelluronium reagent on products' yields and on the direction of the electrophilic intramolecular cyclization of N-alkenyl-2-thioxobenzo(thieno)pyrimidine-4-ones. It was not possible to obtain this electrophile with the reaction of tellurium tetrabromide with benzene containing electron donating group, so it was synthesized by bromination of the corresponding ditelluride in chloroform medium. The interaction between tellurium-containing electrophile and N-alkenyl-2-thioxobenzo(thieno)pyrimidine-4-ones was carried out in glacial acetic acid at room temperature. It has been established that during aryltellurobromination of 3-allyl-quinazoline-2-thione and N-alkenyl thioxo-thieno-pyrimidinones, the annelation of the thiazoline ring takes place, with the formation of a linear condensed system with an exocyclic aryltellurium fragment – hydrobromides of 3-[dibromo(4-ethoxyphenyl)telluromethyl]-2,3-dihydro-5 H -[1,3]thiazolo[2,3-b]quinazolin-5-one, 2-(dibromo(4-ethoxyphenyl)-telluromethyl)-2,3,6,7,8,9-hexahydro-5 H -benzo[4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidin-5-one and 2-methyl-2-(dibromo(4-ethoxyphenyl)-2,3,6,7,8,9-hexahydro-5 H -benzo[4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidine-5-one. The structure of the products of bromotelluro-cyclization is similar to the structure of products of aryltellurochlorination of the corresponding heterocycles. However, the yields of salts with the exocyclic bromoaryltellurium fragment are smaller compared to chloro- analogs. Lower yields of hydrobromides are associated with lower stability of intermediate bromotelluronium cation compared with chlorotelluronium, which is confirmed by theoretical calculations of Gibbs free energy of interaction of aryldihalidetellanium cation with an unsaturated substrate. Computations were performed using DFT level of theory in PRIRODA 17 program with using of GGA PBE functional and 3ζ basis set. The effect of solvent medium (acetic acid) was taken into account using the COSMO model with PM7 Hamiltonian in MOPAC2016 program. The composition and structure of all obtained compounds are proved by elemental analysis and NMR spectra.