Theoretical investigation on synthesis of fused [1,2,3]-triazoloheteroarene via DBU-catalyzed intramolecular azo annulation and 3,4,5-trisubstituted [1,2,4]-triazole via I2‑catalyzed cycloaddition

The mechanism is investigated for DBU-catalyzed intramolecular azo annulation of N-tosylhydrazone and I2‑catalyzed cycloaddition of phenyl tosyl hydrazone with N-phenylbenzamidine. The former contains rate-limiting α-elimination of tosylate facilitated by DBU affording amphiphilic nitrene and intramolecular, 5-endo-trig cyclization forming [1,2,3]-triazoloheteroarene. This method is also applicable for other nonpyridine heteroarene based on enhanced activity of DBU. The latter is composed of eight steps including activation of hydrazone mediated by I2, nucleophilic addition of amidine, intramolecular electron transfer via two times of proton transfer, intramolecular nucleophilic attack followed by third proton transfer achieving ring closure and final reductive elimination of HI, TsNH2 yielding 3,4,5-trisubstituted [1,2,4]-triazole. The rate-limiting step is intramolecular electron transfer under I2 catalysis. The positive solvation effect is suggested by decreased absolute and activation energies in solution compared with in gas. These results are supported by Multiwfn analysis on FMO composition of specific TSs, and MBO value of vital bonding, breaking.