The nitrilimine–alkene cycloaddition is an ultra rapid click reaction

Abstract

The transient formation of nitrilimine in aqueous conditions is greatly influenced by pH and chloride. In basic conditions (pH 10) with no chloride, a diarylnitrilimine precursor readily ionizes to form diarylnitrilimine that reacts almost instantly with an acrylamide-containing protein and fluorescently labels it.

Click Chemistry in Complex Mixtures: Bioorthogonal Bioconjugation

“…This approach has been implemented for the fluorescent modification of oligonucleotides (Gutsmiedl et al, 2009; Singh and Heaney, 2011). While in situ generated nitrile imines are prone to hydrolysis, their 1,3-dipolar cycloaddition is faster and has been applied to the fluorescent labeling of acrylamide containing proteins (Wang et al, 2014). This reaction, however, is strongly influenced by pH and chloride ion concentration.…”

Highly regioselective 1,3-dipolar cycloaddition of diphenylnitrilimine to Sc3N@Ih-C80 affording a very stable, unprecedented pyrazole-ring fused derivative of endohedral metallofullerenes

“…[9][10][11] This is also a powerful tool for the synthesis of various fullerene derivatives with pyrazole rings. 12,13 Since pyrazoles are also a major class of five-membered nitrogen heterocycles in a wide variety of natural products and drug molecules, such structures have received great interest as a result of their broad range of biological activities.…”

Photoinducible Oncometabolite Detection

“…Despite this progress, several challenges remain in the fluorogenic detection of fumarate. In particular, our first‐generation approach suffered from limited sensitivity due to the susceptibility of hydrazonyl chlorides to undergo competing hydrolysis reactions at physiological pH (Figure S1 in the Supporting Information) . This prevented the detection of endogenous fumarate, and instead required exogenous malate be added to cell extracts to amplify FH‐dependent fumarate production .…”