Synthesis and electrophilic heterocyclization of 3-allylsulfanyl-1,2,4-triazino[6,5-b]indole

Abstract

A number of scientific studies has shown that isatin α-thiosemicarbazones, as well as their corresponding cyclization products – [1,2,4]triazino[6,5-b]indole-3-thiones – exhibit higher ionization ability, lipophilicity and anti-inflammatory activity than their isomeric isatin β thiosemicarbazones and their cyclization products. In addition, the well-known indomethacin is characterized by lesser anti-inflammatory activity and greater toxicity than the studied isatin derivatives. At the same time, isatin α thiosemicarbazones and their cyclization products are less described in the literature compared to isatin β thiosemicarbazones and [1,2,4]triazino[5,6-b]indole-3-thiones due to complexity and multi-stage nature of their synthesis. This fact explains the importance of obtaining and studying the properties of new derivatives of these compounds. In the present study, 3-allylsulfanyl-1,2,4-triazino[6,5-b]indole has been synthesized for the first time by the reaction of [1,2,4]triazino[6,5-b]indole-3-thione with allyl bromide in DMF-KOH-H2O medium. It is isomeric in structure to 3-allylsulfanyl-1,2,4-triazino[5,6-b]indole, described in the literature. Taking into consideration that several described derivatives of [1,3]thiazolo and [1,3]thiazino[3',2':2,3][1,2,4]triazino[5,6-b]indole systems showed antimycotic activity, оur further heterocyclization of 3-allylsulfanyl-1,2,4-triazino[6,5-b]indole under the action of iodine and bromine in chloroform is interesting from the point of view of obtaining previously unknown intramolecular salts of [1,3]thiazolo[2ʹ,3ʹ:3,4][1,2,4]triazino[5,6-b]indolium. The structure of the compounds synthesized for the first time was confirmed by the 1H, 13C NMR data, as well as X-ray diffraction.