Annulation-Induced Hidden Reactivity of the 1,2,4-Triazole Backbone

Triazoles are an important class of compounds with widespread applications. Functionalization of the triazole backbone is thus of significant interest. In comparison to 1,2,3-triazoles, C-H activation-functionalization of the congeners 1,2,4-triazoles is surprisingly underdeveloped. Indeed, no such C-H activation-functionalization has been reported for 4-substituted 1,2,4-triazole cores. Furthermore, although denitrogenative ring-opening of 1,2,3-triazoles is well-explored, 1,2,4-triazole/triazolium substrates have not been known to exhibit N-N bond-cleaving ring-opening reactivity so far. In this work, we unveiled an unusual hidden reactivity of the 1,2,4-triazole backbone involving the elusive N-N bond-cleaving ring-opening reaction. This new reactivity was induced by a Satoh-Miura-type C-H activation-annulation at the 1,2,4-triazole motif appended with a pyridine directing group. This unique reaction allowed ready access to a novel class of unsymmetrically substituted 2,2 & PRIME;-dipyridylamines, with one pyridine ring fully-substituted with alkyl groups. The unsymmetrical 2,2 & PRIME;-dipyridylamines were utilized to access unsymmetrical boron-aza-dipyridylmethene fluorescent dyes. Empowered with desirable optical/physical properties such as large Stokes shifts and suitable hydrophobicity arising from optimal alkyl chain length at the fully-substituted pyridine-ring, these dyes were used for intracellular lipid droplet-selective imaging studies, which provided useful information toward designing suitable lipid droplet-selective imaging probes for biomedical applications. An unusual hidden reactivity of the 1,2,4-triazole backbone was unveiled that involves the elusive N-N bond-cleaving ring-opening reaction. This reactivity allows access to a novel class of unsymmetrically substituted 2,2 & PRIME;-dipyridylamines (dpa), which were used to prepare unsymmetrical boron aza-dipyridylmethene fluorescent dyes suitable for intracellular selective lipid droplet imaging studies.image

Automated summary

An unusual hidden reactivity of the 1,2,4-triazole backbone involving the N-N bond-cleaving ring-opening reaction was unveiled. This reaction allowed the synthesis of unsymmetrically substituted 2,2-dipyridylamines and consequently the preparation of unsymmetrical boron aza-dipyridylmethene fluorescent dyes suitable for intracellular selective lipid droplet imaging studies.