Synthesis and Electrophilic Heterocyclization of 3-(Allylsulfanyl)-1,2,4-triazino[6,5-b]indole

A number of studies have shown that isatin α-thiosemicarbazones, as well as their cyclization products, [1,2,4]triazino[6,5-b]indole-3-thiones, exhibit a higher ionization ability, lipophilicity, and anti-inflammatory activity than isomeric β-thiosemicarbazones and their cyclization products. Furthermore, the known drug indomethacin exhibits a lower anti-inflammatory activity and higher toxicity compared to the studied isatin derivatives. At the same time, isatin αthiosemicarbazones and their cyclization products have been explored to a lesser extent than isatin βthiosemicarbazones and [1,2,4]triazino[5,6-b]indole-3-thiones due to the complexity and multistep procedures of their synthesis. This makes the synthesis and study of the properties of new isatin α-thiosemicarbazone derivatives important. In this work, we were the first to synthesize 3-allylsulfanyl-1,2,4-triazino[6,5-b]indole, which is isomeric to previously reported 3-allylsulfanyl-1,2,4-triazino[5,6-b]indole, by the reaction of [1,2,4]triazino[6,5-b]indole-3-thione with allyl bromide in DMF in the presence of aqueous potassium hydroxide. Taking into account that some known [1,3]thiazolo- and [1,3]thiazino[3′,2′:2,3][1,2,4]triazino[5,6b]indole derivatives showed antimycotic activity, 3allylsulfanyl-1,2,4-triazino[6,5-b]indole was further cyclized by the action of iodine and bromine in chloroform to obtain previously unknown [1,3]thiazolo[2′,3′:3,4][1,2,4]triazino[6,5-b]indolium salts. The structure of the newly synthesized compounds was confirmed by 1H and 13C NMR spectra, and the molecular structure of 3-(bromomethyl)-2,3-dihydro-6H-[1,3]thiazolo[2′,3′:3,4][1,2,4]triazino[5,6-b]indolium bromide was determined by X-ray analysis.