Water‐Involved Ring‐Opening of 4‐Phenyl‐1,2,4‐triazoline‐3,5‐dione for “Photo‐Clicked” Access to Carbamoyl Formazan Photoswitches In Situ

Abstract

Cyclic azodicarbonyl derivatives, particularly 4phenyl-1,2,4-triazoline-3,5-dione (PTAD), commonly serve as arenophile, dienophile, enophile and electrophile. Perplexed by its instability in aqueous environment, there are few studies focused on the transient intermediate produced by hydrolysis of PTAD to achieve synthetic significance. Herein, we describe a "photo-click" method that involves nitrile imine (NI) from diarylsydnone to capture the diazenecarbonylphenyl-carbamic acid (DACPA) generated by water-promoted ring-opening of PTAD. DFT calculation reveal that H-bonding interactions between PTAD and water are vital to form DACPA which exhibited an umpolung effect during ligation by nature bond orbit (NBO) analysis. The ultra-fast ligation resulted in carbamoyl formazans, as a unique Z $ E photoswitchable linker on target molecules, including peptide and drugs, with excellent anti-fatigue performance. This strategy is showcased to construct highly functionalized carbamoyl formazans in situ for photo-pharmacology and material studies, which also expands the chemistry of PTAD in aqueous media.

Rapid construction of bicyclic triazoline skeletons with dual-state emissionviacycloaddition reaction of 4-phenyl-1,2,4-triazoline-3,5-dione with vinyl azides

“…A plausible reaction mechanism was also proposed based on previous research 17 and calculations, as shown in Fig. 5b.…”

“…4-Phenyl-1,2,4-triazoline-3,5-dione (PTAD) has served as a highly reactive dienophile or electrophile in various chemical transformations, 17 and has been utilized for bioconjugation of tyrosine 18 and tryptophan 19 residues on proteins. Back in 1976, 20 vinyl azides (VAs) were utilized as diene surrogates for ring formations with PTAD, affording a unique bicyclic triazoline 20 in which the electron-deficient –NN– moiety in the PTAD was transformed into an electron-rich dihydrazide kernel.…”