The scientific work is devoted to the elucidation of the reactions of electrophilic heterocyclization of (S)N-alkenyl(alkynyl) substituted 2-thioquinazoline-4-ones under the action of halogens, selenium and tellurium tetrahalides, p-alkoxyphenyltellurium trichlorides and proton-containing electrophilic reagents, development of convenient methods for the directed synthesis of thiazolo(thiazino, thiazepino)annelated condensed systems based on quinazoline and study of their chemical and biological properties. The I section summarizes the literature data concerning the reactions of electrophilic cyclization of N(S)-alkenyl(alkynyl) quinazoline and pyrimidine-4-one derivatives with such electrophilic reagents as halogens, aryltellurium trichlorides and acids. The II section presents the results of the author's research on the electrophilic heterocyclicization of S(N)-alkenyl(alkynyl) derivatives of 2-thioquinazoline-4-ones and the microbiological properties of the synthesized condensed quinazoline heterocycles, including the first one: The region-direction of electrophilic heterocyclization of 2-S-allyl(methallyl, dimethylallyl, cynnamyl, propargyl, butynyl, pentynyl) and 3-N-allyl(methallyl) derivatives of 2-thioquinazoline-4-one under the action of halogens, chalcogen tetrahalides, aryltellurium trichloride, protonic acids and the influence of structural and electronic factors of the starting substrates and reaction conditions on the course of heteroannelation reactions was determined.
The direction of halogenation of 2-S-allyl thioethers of quinazoline-4(3H)-one has been determined to depend on the presence of a substituent at the terminal carbon atom of the allyl fragment. In the case of terminally unsubstituted allyl (methallyl) and dimethylallyl thioethers, the thiazole cycle is annelated to the quinazoline backbone, and in the case of cynnamyl thioethers, the thiazine cycle is annelated. By varying the presence and type of substituent at the terminal allyl carbon, the direction of halogenation can be controlled. It was found that the regiochemistry of the chalcogen-induced cyclization of allyl, methallyl and dimethylallyl thioethers of quinazoline-4-one does not depend on the nature of the electrophilic reagent and leads to the formation of thiazolinoquinazolinium salts. In the case of quinazoline-4-one cynnamyl thioethers, halogen- and selenium-induced cyclization occurs with annelation of the thiazine cycle, and during telluriumhalogenation, adducts with a six-coordinated tellurium atom are formed. It was found that the stereoselectivity of halogenation of quinazoline terminal alkynyl thioethers depends on the length of the alkynyl substituent and the polarity of the solvent. Propargyl thioethers undergo stereoselective halogenated cyclization in acetic acid, while stereoselectivity decreases in chloroform. In contrast, butynyl and pentynyl quinazoline thioethers undergo regio- and stereoselective cyclization under the action of halogens to form halide salts of halogenomethylidene substituted thiazino(thiazepino)quinazolines of E-configuration regardless of the polarity of the solvent. Trihalogenochalcogenomethylidene-substituted thiazolinoquinazolones of E-configuration were synthesized for the first time by electrophilic heterocyclization of 2-propargylthioquinazolinones under the action of chalcogen tetrahalogenides and p-alkoxyphenyltellurium trichlorides. It was found that the regiochemistry of halogen-, proton- and chalcogen-induced heterocyclization of 3-alkenyl-2-thioxoquinazolin-4-ones leads to the formation of 2-functionalized dihydrothiazolo[2,3-b]quinazolines in the form of both salts and bases. The regiochemistry of the anelation of the thiazoline ring to the quinazoline nucleus remains unchanged and does not depend on the specifics of the electrophilic reagent used, which provides flexibility in choosing the most optimal electrophilic reagent from a wide range of available options, while maintaining the desired chemoselectivity of the reaction. It was found that the S-allyl fragment and the endocyclic nitrogen of position 1 of quinazoline are more active reaction site for halogen- and chalcogen-induced heterocyclization in S,N-diallylquinazoline-4-ones. The inertness of the N-allyl fragment in the reaction, even in the presence of excess halogen, is probably explained by a kinetic factor.
The antibacterial and antifungal activity of the newly synthesized condensed quinazoline derivatives was revealed, and determined structural dependencies allow to search the most bioactive derivatives in a series of condensed quinazolines.
On the basis of 4-ethyl-1-(iodomethyl)-1-methyl-5-oxo-1,2,4,5-tetrahydrothiazolo[3,2-a]quinazolin-10-ium triiodide, an analytical sensor for the determination of vitamin C in beverages, juices and pharmaceuticals by potentiometric titration was developed. The III section contains the synthesis techniques and physicochemical characteristics of the obtained compounds.
