Síntese de tiazóis fundidos a partir de indeno e β-dicetonas cíclicas promovida por ácido tribromoisocianúrico: uma abordagem telescópica

Abstract

In this work, the use of tribromoisocyanuric acid (TBCA) was explored for the in situ formation of α-bromocarbonyl intermediates in the telescoped synthesis of 2-aminothiazoles fused to partially saturated rings, which have gained increasing interest in medicinal and agrochemical chemistry. Seven examples of 2-amino-5,6-dihydrobenzo[d]thiazol-7(4H)-ones were synthesized in 15–83% yield through the bromination reaction of dimedone or 1,3-cyclohexanedione with TBCA catalyzed by p-toluenesulfonic acid, followed by the Hantzsch reaction with thioureas, without the isolation of any reaction intermediates, thus saving one isolation step. The telescoped synthesis of 13 examples of 2-aminoindenothiazoles was achieved by reacting indene with TBCA, promoting sequential co-bromination/oxidation reactions in water, followed by reaction with various monosubstituted thioureas, affording the heterocycles in 19–57% yield after a single isolation step. This reaction was evaluated in comparison with other current methodologies and classical routes using green metrics such as atom economy (AE), atomic efficiency (AEf), reaction mass efficiency (RME), and optimization efficiency (OE). It was demonstrated that, for selected cases, the difference between stepwise synthesis and telescoped synthesis resulted in 42–148% higher final product yield for the step-economical process. In vitro and in vivo assays (in soybean seedlings) were performed with the synthesized fused thiazoles to evaluate their activity against Meloidogyne incognita at its second juvenile stage, a highly damaging plant-parasitic nematode affecting commercially important crops. Among the investigated compounds, N-(pyridin-2-yl)-8Hindeno[1,2-d]thiazol-2-amine exhibited nematicidal activity comparable to that of a commercially used substance, with low phytotoxicity, making it a promising candidate for the development of new nematicides.