Chemical Waltz of Organic Molecules "On Water": Saline-Assisted Sustainable Regioselective Synthesis of Fluorogenic Heterobioconjugates via Click Reaction.

Abstract

A new sustainable green protocol for obtaining highly fluorogenic heterobioconjugates by a well-known copper-mediated azide–alkyne cycloaddition click reaction of nonfluorescent 3-azidocoumarins/benzyl azides (2a–f) and terminal alkynes (1a–e) using aqueous NaCl as a cheap and nontoxic salting-out agent under ultrasonication at ambient temperature is described. The presence of aqueous NaCl significantly influences the reaction by disturbing the water kosmotropes and augments the hydrophobic interaction of water-insoluble reactants, thus making the reaction feasible in water at neutral pH. The “beauty” of the presented ecofriendly approach is further boosted up by recycling the aqueous filtrate of the reaction mixture without further addition of NaCl, CuSO4·5H2O, and Na ascorbate up to seven cycles, resulting in effectively low copper loading (100 ppm) with excellent turn-over number (4850) and turn-over frequency (88.18 min–1). A gram-scale synthesis was also successfully achieved with 92% yield, further elaborating the scope of this methodology.