CHALCOGENATION OF N-ALKENYL DERIVATIVES OF 2-THIOXO-2,3-DIHYDRO QUINAZOLINE-4(1H)-ONE

Abstract

Oxo- and thio-substituted quinazolines are promising biologically active objects. A special place in a number of quinazolines is occupied by its condensed analogues, namely thiazoloquinazolines, which exhibit antioxidant, antimicrobial and antitumor activity. An effective method for the synthesis of condensed quinazoline derivatives is electrophilic intramolecular cyclization of its unsaturated derivatives. The usage of pharmacoformic chalcogen-containing electrophiles in these reactions has been insufficiently studied. Organochalcogen-containing heterocyclic compounds are the promising biologically active substances with different pharmacological action. Therefore, the study of reactions of electrophilic intramolecular cyclization of N(3)-alkenyl derivatives of 2-thioxo-2,3-dihydroquinazolin-4(1H)-one under the action of chalcogen tetrahalides is an urgent task.
 N (3)-alkenyl derivatives of 2,3-dihydroquinazolin-4(1H)-one were used as the object of study. It was found that the interaction of tellurium tetrabromide with N(3)-alkenyl-2-thioxoquinazolin-4-ones in glacial acetic acid leads to linear hydrobromides of 2-[(tribromotelluro) methyl]-2,3-dihydro-5H-[1,3]thiazolo[2,3-b]quinazolin-5-one.
 In the reaction with N(3)-methallyl-2-thioxo-2,3-dihydroquinazolin-4(1H)-one, individual tellurium tetrachloride was used, which was obtained by passing chlorine over the tellurium. It is proved that halotellurium-induced cyclization of N-methallyl quinazolone with tellurium tetrachloride occurs regioselectively with the formation of 2-methyl-2-[(trichlorotelluro)methyl]-2,3-dihydro-5H- [1,3]thiazolo[2,3-b]quinazoline-5-one hydrochloride of linear structure.
 In order to study the influence of the nature of chalcogen in the electrophilic reagent on the regiochemistry of cyclization in the reaction with N(3)-methallyl-2-thioxo-2,3-dihydroquinazolin-4(1H)-one, obtained in situ selenium tetrachloride was used. The selenochlorination reaction of N(3)-methallyl-2-thioxo-2,3-dihydroquinazolin-4(1H)-one in chloroform gave a linear hydrochloride of 2-methyl-2-[(trichloroseleno)methyl]-2,3-dihydro-5H-[1,3]thiazolo[2,3-b]quinazolin-5-one.
 Thus, the regiochemistry of electrophilic intramolecular cyclization of N(3)-alkenyl-2-thioxo-2,3-dihydroquinazolin-4(1H)-ones by chalcogentetrahalides was investigated and it was proved that the annulationof the thiazoline cycle occurs with the formation of bioperspective bundles of tricyclic heterocycles of linear constitution independently from nature and origin of electrophilic reagent.